Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
July-2026 Volume 34 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
July-2026 Volume 34 Issue 1

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Review Open Access

Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review)

  • Authors:
    • Shilin Zhang
    • Zhenhua Li
    • Li Fu
  • View Affiliations / Copyright

    Affiliations: School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, P.R. China, Department of Pathology, Shanghai Clinical Research and Trial Center, ShanghaiTech University, Shanghai 201210, P.R. China, School of Life Science and Technology, ShanghaiTech University, Shanghai 201210, P.R. China
    Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 186
    |
    Published online on: May 4, 2026
       https://doi.org/10.3892/mmr.2026.13896
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:


Abstract

Proline‑ and glutamine‑rich splicing factor (SFPQ) is an RNA‑binding protein that is predominantly localized in the nucleus and plays a multifaceted regulatory role in the process of gene expression. The functions of SFPQ include the promotion or inhibition of gene transcription, pre‑mRNA splicing, mRNA processing, transport and localization, and translation. The primary impact of SFPQ on cellular processes is the regulation of cell cycle progression and apoptosis. In addition, SFPQ represents an important element of paraspeckles, exerting a notable influence on gene expression within the nucleus. The expression of SFPQ is altered in tumors, promoting the development and drug resistance of tumors in various ways, notably altering the prognosis of patients. In the present review, the fundamental physiological functions of SFPQ and its particular effects on tumorigenesis and development are discussed.
View Figures

Figure 1

Domain structure of SFPQ. The
schematic illustrates key functional domains within the SFPQ
protein. Each domain is identified by its name and the range of
amino acid residues it encompasses (numbers indicated above each
domain boundary). The depicted domains are important for protein
and RNA binding, dimerization and phase separation. PrLD,
prion-like domain; LLPS, liquid-liquid phase separation; RRM, RNA
recognition motif; NOPS, NONA/paraspeckle structural domain; NLS,
nuclear localization sequence; SFPQ, proline- and glutamine rich
splicing factor.

Figure 2

Mechanism of SFPQ regulating gene
expression. A, SFPQ recruits epigenetic regulators, such as SIN3A
and HDAC, and represses gene expression. B, SFPQ undergoes
liquid-liquid phase separation with some transcriptional factors,
such as Smad4, thereby inhibiting gene expression mediated by the
Smad complex. C, SFPQ regulates alternative splicing. D, SFPQ is an
important component of paraspeckles, which responds to stress
conditions by RNA editing and RNA nuclear retention. E, SFPQ
mediates mRNA editing and subcellular localization. F, SFPQ takes
part in DNA repair. G, SFPQ is also a component of stress granule.
Created in https://BioRender.com. SFPQ, proline-
and glutamine-rich splicing factor; HDAC, histone deacetylase;
SIN3A, paired amphipathic helix protein Sin3a; TF, transcriptional
factor; P, phosphate group; NONO, non-POU domain-containing
octamer-binding protein; FUS, RNA-binding protein FUS; RBP, RNA
binding protein.

Figure 3

A schematic representation of SFPQ
regulating transcription in cancer. The schematic depicts the
differential regulatory effects of SFPQ on gene expression in NSCLC
(top panels) and GBM (bottom panels) under normoxic and hypoxic
conditions. Created in https://BioRender.com. NSCLC, non-small cell lung
cancer; GBM, glioblastoma; LHFPL3-AS2, LHFPL tetraspan subfamily
member 3-antisense RNA 2; TXNIP, thioredoxin-interacting protein;
ALKBH5, alkylated DNA repair protein alkB homolog 5; NEAT1,
nucleus-enriched abundant transcript 1; CXCL8, C-X-C motif
chemokine ligand 8; SFPQ, proline- and glutamine-rich splicing
factor; m6A, N6-methyladenosine.

Figure 4

A schematic representation of SFPQ
regulating alternative splicing in cancer. (A) In normal liver
tissue, the long isoform of BIN1 is expressed at high levels and
suppresses c-Myc-induced downstream gene expression. In HCC,
upregulated SFPQ promotes exon 12a inclusion in BIN1 pre-mRNA,
shifting the BIN1 isoform balance towards the long isoform. This
increased abundance of the long BIN1 isoform stabilizes PLK1,
thereby promoting tumorigenesis. (B) In BCa, downregulation of SFPQ
promotes skipping of the second exon of SETMAR, increasing the
proportion of the short SETMAR isoform. This isoform shift reduces
H3K27me3 levels, leading to enhanced expression of
pro-metastatic genes and promoting metastasis. (C) In
platinum-resistant ovarian cancer cells, upregulated SFPQ mediates
the skipping of exons 4–7 in caspase-9 pre-mRNA. This promotes
accumulation of the anti-apoptotic long isoform of caspase-9,
resulting in enhanced cell survival. Created in https://BioRender.com. HCC, hepatocellular carcinoma;
BCa, bladder cancer; BIN1, bridging integrator 1; BIN1-S, BIN1
short isoform; BIN1-L, BIN1 long isoform; NONO, non-POU
domain-containing octamer binding; SETMAR, SET domain and mariner
transposase fusion gene; SETMAR-S, SETMAR short isoform; SETMAR-L,
SETMAR long isoform; SETD7, SET domain containing 7; PRDX4,
peroxiredoxin 4; GANAB, glucosidase II α subunit; SRSF2, serine and
arginine rich splicing factor 2; SFPQ, proline- and glutamine-rich
splicing factor; DHX9, ATP-dependent RNA helicase A; 12a, exon 12a
of c-Myc; PLK1, serine/threonine-protein kinase PLK1; caspase 9-S,
caspase 9 short isoform; caspase 9-L, caspase 9 long isoform;
H3K27me3, histone 3 lysine residue 27
trimethylation.
View References

1 

Patton JG, Porro EB, Galceran J, Tempst P and Nadal-Ginard B: Cloning and characterization of PSF, a novel pre-mRNA splicing factor. Genes Dev. 7:393–406. 1993. View Article : Google Scholar : PubMed/NCBI

2 

Dong B, Horowitz DS, Kobayashi R and Krainer AR: Purification and cDNA cloning of HeLa cell p54nrb, a nuclear protein with two RNA recognition motifs and extensive homology to human splicing factor PSF and Drosophila NONA/BJ6. Nucleic Acids Res. 21:4085–4092. 1993. View Article : Google Scholar : PubMed/NCBI

3 

Prasanth KV, Prasanth SG, Xuan Z, Hearn S, Freier SM, Bennett CF, Zhang MQ and Spector DL: Regulating gene expression through RNA nuclear retention. Cell. 123:249–263. 2005. View Article : Google Scholar : PubMed/NCBI

4 

Dye BT and Patton JG: An RNA recognition motif (RRM) is required for the localization of PTB-associated splicing factor (PSF) to subnuclear speckles. Exp Cell Res. 263:131–144. 2001. View Article : Google Scholar : PubMed/NCBI

5 

Shav-Tal Y, Cohen M, Lapter S, Dye B, Patton JG, Vandekerckhove J and Zipori D: Nuclear relocalization of the pre-mRNA splicing factor PSF during apoptosis involves hyperphosphorylation, masking of antigenic epitopes, and changes in protein interactions. Mol Biol Cell. 12:2328–2340. 2001. View Article : Google Scholar : PubMed/NCBI

6 

Shav-Tal Y, Blechman J, Darzacq X, Montagna C, Dye BT, Patton JG, Singer RH and Zipori D: Dynamic sorting of nuclear components into distinct nucleolar caps during transcriptional inhibition. Mol Biol Cell. 16:2395–2413. 2005. View Article : Google Scholar : PubMed/NCBI

7 

Zhang Z and Carmichael GG: The fate of dsRNA in the nucleus: A p54(nrb)-containing complex mediates the nuclear retention of promiscuously A-to-I edited RNAs. Cell. 106:465–475. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Sharathchandra A, Lal R, Khan D and Das S: Annexin A2 and PSF proteins interact with p53 IRES and regulate translation of p53 mRNA. RNA Biol. 9:1429–1439. 2012. View Article : Google Scholar : PubMed/NCBI

9 

Emili A, Shales M, McCracken S, Xie W, Tucker PW, Kobayashi R, Blencowe BJ and Ingles CJ: Splicing and transcription-associated proteins PSF and p54nrb/nonO bind to the RNA polymerase II CTD. RNA. 8:1102–1111. 2002. View Article : Google Scholar : PubMed/NCBI

10 

Wu X, Yoo Y, Okuhama NN, Tucker PW, Liu G and Guan JL: Regulation of RNA-polymerase-II-dependent transcription by N-WASP and its nuclear-binding partners. Nat Cell Biol. 8:756–763. 2006. View Article : Google Scholar : PubMed/NCBI

11 

Ferrai C, Naum-Onganía G, Longobardi E, Palazzolo M, Disanza A, Diaz VM, Crippa MP, Scita G and Blasi F: Induction of HoxB transcription by retinoic acid requires actin polymerization. Mol Biol Cell. 20:3543–3551. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Mathur M, Tucker PW and Samuels HH: PSF is a novel corepressor that mediates its effect through Sin3A and the DNA binding domain of nuclear hormone receptors. Mol Cell Biol. 21:2298–2311. 2001. View Article : Google Scholar : PubMed/NCBI

13 

Dong X, Sweet J, Challis JR, Brown T and Lye SJ: Transcriptional activity of androgen receptor is modulated by two RNA splicing factors, PSF and p54nrb. Mol Cell Biol. 27:4863–4875. 2007. View Article : Google Scholar : PubMed/NCBI

14 

Duong HA, Robles MS, Knutti D and Weitz CJ: A molecular mechanism for circadian clock negative feedback. Science. 332:1436–1439. 2011. View Article : Google Scholar : PubMed/NCBI

15 

Dong L, Zhang X, Fu X, Zhang X, Gao X, Zhu M, Wang X, Yang Z, Jensen ON, Saarikettu J, et al: PTB-associated splicing factor (PSF) functions as a repressor of STAT6-mediated Ig epsilon gene transcription by recruitment of HDAC1. J Biol Chem. 286:3451–3459. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Imamura K, Imamachi N, Akizuki G, Kumakura M, Kawaguchi A, Nagata K, Kato A, Kawaguchi Y, Sato H, Yoneda M, et al: Long Noncoding RNA NEAT1-Dependent SFPQ relocation from promoter region to paraspeckle mediates IL8 Expression upon immune stimuli. Mol Cell. 54:10552014. View Article : Google Scholar : PubMed/NCBI

17 

Wang G, Cui Y, Zhang G, Garen A and Song X: Regulation of proto-oncogene transcription, cell proliferation, and tumorigenesis in mice by PSF protein and a VL30 noncoding RNA. Proc Natl Acad Sci USA. 106:16794–16798. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Heyd F and Lynch KW: PSF controls expression of histone variants and cellular viability in thymocytes. Biochem Biophys Res Commun. 414:743–749. 2011. View Article : Google Scholar : PubMed/NCBI

19 

Ha K, Takeda Y and Dynan WS: Sequences in PSF/SFPQ mediate radioresistance and recruitment of PSF/SFPQ-containing complexes to DNA damage sites in human cells. DNA Repair (Amst). 10:252–259. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Morozumi Y, Takizawa Y, Takaku M and Kurumizaka H: Human PSF binds to RAD51 and modulates its homologous-pairing and strand-exchange activities. Nucleic Acids Res. 37:4296–4307. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Rajesh C, Baker DK, Pierce AJ and Pittman DL: The splicing-factor related protein SFPQ/PSF interacts with RAD51D and is necessary for homology-directed repair and sister chromatid cohesion. Nucleic Acids Res. 39:132–145. 2011. View Article : Google Scholar : PubMed/NCBI

22 

Salton M, Lerenthal Y, Wang SY, Chen DJ and Shiloh Y: Involvement of Matrin 3 and SFPQ/NONO in the DNA damage response. Cell Cycle. 9:1568–1576. 2010. View Article : Google Scholar : PubMed/NCBI

23 

Melton AA, Jackson J, Wang J and Lynch KW: Combinatorial control of signal-induced exon repression by hnRNP L and PSF. Mol Cell Biol. 27:6972–6984. 2007. View Article : Google Scholar : PubMed/NCBI

24 

King HA, Cobbold LC, Pichon X, Pöyry T, Wilson LA, Booden H, Jukes-Jones R, Cain K, Lilley KS, Bushell M and Willis AE: Remodelling of a polypyrimidine tract-binding protein complex during apoptosis activates cellular IRESs. Cell Death Differ. 21:161–171. 2014. View Article : Google Scholar : PubMed/NCBI

25 

Tsukahara T, Matsuda Y and Haniu H: PSF knockdown enhances apoptosis via downregulation of LC3B in human colon cancer cells. Biomed Res Int. 2013:2049732013. View Article : Google Scholar : PubMed/NCBI

26 

Tsukahara T, Haniu H and Matsuda Y: PTB-associated splicing factor (PSF) is a PPARγ-binding protein and growth regulator of colon cancer cells. PLoS One. 8:e587492013. View Article : Google Scholar : PubMed/NCBI

27 

Cho S, Moon H, Loh TJ, Oh HK, Williams DR, Liao DJ, Zhou J, Green MR, Zheng X and Shen H: PSF contacts exon 7 of SMN2 pre-mRNA to promote exon 7 inclusion. Biochim Biophys Acta. 1839:517–525. 2014. View Article : Google Scholar : PubMed/NCBI

28 

Ke YD, Dramiga J, Schütz U, Kril JJ, Ittner LM, Schröder H and Götz J: Tau-mediated nuclear depletion and cytoplasmic accumulation of SFPQ in Alzheimer's and Pick's disease. PLoS One. 7:e356782012. View Article : Google Scholar : PubMed/NCBI

29 

Kok VJT, Tang JY, Eng GWL, Tan SY, Chin JTF, Quek CH, Lai WX, Lim TK, Lin Q, Chua JJE and Cheong JK: SFPQ promotes RAS-mutant cancer cell growth by modulating 5′-UTR mediated translational control of CK1α. NAR Cancer. 4:zcac0272022. View Article : Google Scholar : PubMed/NCBI

30 

Yang L, Yang J, Jacobson B, Gilbertsen A, Smith K, Higgins L, Guerrero C, Xia H, Henke CA and Lin J: SFPQ promotes lung cancer malignancy via regulation of CD44 v6 expression. Front Oncol. 12:8622502022. View Article : Google Scholar : PubMed/NCBI

31 

Yang L, Gilbertsen A, Jacobson B, Pham J, Fujioka N, Henke CA and Kratzke RA: SFPQ and Its Isoform as Potential Biomarker for Non-Small-Cell Lung Cancer. Int J Mol Sci. 24:125002023. View Article : Google Scholar : PubMed/NCBI

32 

Lin Y, Zhong W, Lin Q, Ye Y, Li S, Chen H, Liu H, Xu L, Zhuang W, Chen S, et al: SFPQ promotes the proliferation, migration and invasion of hepatocellular carcinoma cells and is associated with poor prognosis. Am J Cancer Res. 13:2269–2284. 2023.PubMed/NCBI

33 

Xiao M, Wang F, Chen N, Zhang H, Cao J, Yu Y, Zhao B, Ji J, Xu P, Li L, et al: Smad4 sequestered in SFPQ condensates prevents TGF-β tumor-suppressive signaling. Dev Cell. 59:48–63.e8. 2024. View Article : Google Scholar : PubMed/NCBI

34 

Yarosh CA, Iacona JR, Lutz CS and Lynch KW: PSF: Nuclear busy-body or nuclear facilitator? Wiley Interdiscip Rev RNA. 6:351–367. 2015. View Article : Google Scholar : PubMed/NCBI

35 

Fox AH, Bond CS and Lamond AI: P54nrb forms a heterodimer with PSP1 that localizes to paraspeckles in an RNA-dependent manner. Mol Biol Cell. 16:5304–5315. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Kuwahara S, Ikei A, Taguchi Y, Tabuchi Y, Fujimoto N, Obinata M, Uesugi S and Kurihara Y: PSPC1, NONO, and SFPQ are expressed in mouse Sertoli cells and may function as coregulators of androgen receptor-mediated transcription. Biol Reprod. 75:352–359. 2006. View Article : Google Scholar : PubMed/NCBI

37 

Thandapani P, O'Connor TR, Bailey TL and Richard S: Defining the RGG/RG motif. Mol Cell. 50:613–623. 2013. View Article : Google Scholar : PubMed/NCBI

38 

Kiledjian M and Dreyfuss G: Primary structure and binding activity of the hnRNP U protein: Binding RNA through RGG box. EMBO J. 11:2655–2664. 1992. View Article : Google Scholar : PubMed/NCBI

39 

Maris C, Dominguez C and Allain FH: The RNA recognition motif, a plastic RNA-binding platform to regulate post-transcriptional gene expression. FEBS J. 272:2118–2131. 2005. View Article : Google Scholar : PubMed/NCBI

40 

Cléry A, Sinha R, Anczuków O, Corrionero A, Moursy A, Daubner GM, Valcárcel J, Krainer AR and Allain FH: Isolated pseudo-RNA-recognition motifs of SR proteins can regulate splicing using a noncanonical mode of RNA recognition. Proc Natl Acad Sci USA. 110:E2802–E2811. 2013. View Article : Google Scholar : PubMed/NCBI

41 

Passon DM, Lee M, Rackham O, Stanley WA, Sadowska A, Filipovska A, Fox AH and Bond CS: Structure of the heterodimer of human NONO and paraspeckle protein component 1 and analysis of its role in subnuclear body formation. Proc Natl Acad Sci USA. 109:4846–4850. 2012. View Article : Google Scholar : PubMed/NCBI

42 

Sasaki YT and Hirose T: How to build a paraspeckle. Genome Biol. 10:2272009. View Article : Google Scholar : PubMed/NCBI

43 

Jacobs FM, van Erp S, van der Linden AJ, von Oerthel L, Burbach JP and Smidt MP: Pitx3 potentiates Nurr1 in dopamine neuron terminal differentiation through release of SMRT-mediated repression. Development. 136:531–540. 2009. View Article : Google Scholar : PubMed/NCBI

44 

Saud K, Cánovas J, Lopez CI, Berndt FA, López E, Maass JC, Barriga A and Kukuljan M: SFPQ associates to LSD1 and regulates the migration of newborn pyramidal neurons in the developing cerebral cortex. Int J Dev Neurosci. 57:1–11. 2017. View Article : Google Scholar : PubMed/NCBI

45 

Gao Z, Chen M, Tian X, Chen L, Chen L, Zheng X, Wang H, Chen J, Zhao A, Yao Q, et al: A novel human lncRNA SANT1 cis-regulates the expression of SLC47A2 by altering SFPQ/E2F1/HDAC1 binding to the promoter region in renal cell carcinoma. RNA Biol. 16:940–949. 2019. View Article : Google Scholar : PubMed/NCBI

46 

Dong J, Pervaiz W, Tayyab B, Li D, Kang L, Zhang H, Gong H, Ma X, Li J, Agboyibor C, et al: A comprehensive comparative study on LSD1 in different cancers and tumor specific LSD1 inhibitors. Eur J Med Chem. 240:1145642022. View Article : Google Scholar : PubMed/NCBI

47 

Lopez CI, Saud KE, Aguilar R, Berndt FA, Cánovas J, Montecino M and Kukuljan M: The chromatin modifying complex CoREST/LSD1 negatively regulates notch pathway during cerebral cortex development. Dev Neurobiol. 76:1360–1373. 2016. View Article : Google Scholar : PubMed/NCBI

48 

Cai W, Xiao C, Fan T, Deng Z, Wang D, Liu Y, Li C and He J: Targeting LSD1 in cancer: Molecular elucidation and recent advances. Cancer Lett. 598:2170932024. View Article : Google Scholar : PubMed/NCBI

49 

Hirose T, Virnicchi G, Tanigawa A, Naganuma T, Li R, Kimura H, Yokoi T, Nakagawa S, Bénard M, Fox AH and Pierron G: NEAT1 long noncoding RNA regulates transcription via protein sequestration within subnuclear bodies. Mol Biol Cell. 25:169–183. 2014. View Article : Google Scholar : PubMed/NCBI

50 

Urban RJ, Bodenburg Y, Kurosky A, Wood TG and Gasic S: Polypyrimidine tract-binding protein-associated splicing factor is a negative regulator of transcriptional activity of the porcine p450scc insulin-like growth factor response element. Mol Endocrinol. 14:774–782. 2000. View Article : Google Scholar : PubMed/NCBI

51 

Cheng Z, Lu C, Wang H, Wang N, Cui S, Yu C, Wang C, Zuo Q, Wang S, Lv Y, et al: Long noncoding RNA LHFPL3-AS2 suppresses metastasis of non-small cell lung cancer by interacting with SFPQ to regulate TXNIP expression. Cancer Lett. 531:1–13. 2022. View Article : Google Scholar : PubMed/NCBI

52 

Ma H, Han P, Ye W, Chen H, Zheng X, Cheng L, Zhang L, Yu L, Wu X, Xu Z, et al: The long Noncoding RNA NEAT1 exerts antihantaviral effects by acting as positive feedback for RIG-I signaling. J Virol. 91:e02250–16. 2017. View Article : Google Scholar : PubMed/NCBI

53 

Dong F, Qin X, Wang B, Li Q, Hu J, Cheng X, Guo D, Cheng F, Fang C, Tan Y, et al: ALKBH5 facilitates hypoxia-induced paraspeckle assembly and IL8 secretion to generate an immunosuppressive tumor microenvironment. Cancer Res. 81:5876–5888. 2021. View Article : Google Scholar : PubMed/NCBI

54 

Rosonina E, Ip JY, Calarco JA, Bakowski MA, Emili A, McCracken S, Tucker P, Ingles CJ and Blencowe BJ: Role for PSF in mediating transcriptional activator-dependent stimulation of pre-mRNA processing in vivo. Mol Cell Biol. 25:6734–6746. 2005. View Article : Google Scholar : PubMed/NCBI

55 

Mora Gallardo C, Sánchez de Diego A, Gutiérrez Hernández J, Talavera-Gutiérrez A, Fischer T, Martínez AC and van Wely KHM: Dido3-dependent SFPQ recruitment maintains efficiency in mammalian alternative splicing. Nucleic Acids Res. 47:5381–5394. 2019. View Article : Google Scholar : PubMed/NCBI

56 

Kim J, Lee Y, Jeon T, Ju S, Kim JS, Kim MS and Kang C: Autophagy-dependent splicing control directs translation toward inflammation during senescence. Dev Cell. 60:364–378.e7. 2025. View Article : Google Scholar : PubMed/NCBI

57 

Hu Z, Dong L, Li S, Li Z, Qiao Y, Li Y, Ding J, Chen Z, Wu Y, Wang Z, et al: Splicing Regulator p54(nrb)/Non-POU domain-containing octamer-binding protein enhances carcinogenesis through oncogenic isoform switch of MYC box-dependent interacting protein 1 in hepatocellular carcinoma. Hepatology. 72:548–568. 2020. View Article : Google Scholar : PubMed/NCBI

58 

Bernard A, Hibos C, Richard C, Viltard E, Chevrier S, Lemoine S, Melin J, Humblin E, Mary R, Accogli T, et al: The tumor microenvironment impairs Th1 IFNγ secretion through alternative splicing modifications of Irf1 Pre-mRNA. Cancer Immunol Res. 9:324–336. 2021. View Article : Google Scholar : PubMed/NCBI

59 

Xie R, Chen X, Cheng L, Huang M, Zhou Q, Zhang J, Chen Y, Peng S, Chen Z, Dong W, et al: NONO inhibits lymphatic metastasis of bladder cancer via alternative splicing of SETMAR. Mol Ther. 29:291–307. 2021. View Article : Google Scholar : PubMed/NCBI

60 

An Y and Duan H: The role of m6A RNA methylation in cancer metabolism. Mol Cancer. 21:142022. View Article : Google Scholar : PubMed/NCBI

61 

Wang T, Kong S, Tao M and Ju S: The potential role of RNA N6-methyladenosine in Cancer progression. Mol Cancer. 19:882020. View Article : Google Scholar : PubMed/NCBI

62 

Song H, Wang Y, Wang R, Zhang X, Liu Y, Jia G and Chen PR: SFPQ Is an FTO-binding protein that facilitates the demethylation substrate preference. Cell Chem Biol. 27:283–291.e6. 2020. View Article : Google Scholar : PubMed/NCBI

63 

Thivierge C, Bellefeuille M, Diwan SS, Dyakov BJA, Leventis R, Perron G, Najafabadi HS, Gravel SP, Gingras AC and Duchaine TF: Paraspeckle-independent co-transcriptional regulation of nuclear microRNA biogenesis by SFPQ. Cell Rep. 43:1146952024. View Article : Google Scholar : PubMed/NCBI

64 

Bottini S, Hamouda-Tekaya N, Mategot R, Zaragosi LE, Audebert S, Pisano S, Grandjean V, Mauduit C, Benahmed M, Barbry P, et al: Post-transcriptional gene silencing mediated by microRNAs is controlled by nucleoplasmic Sfpq. Nat Commun. 8:11892017. View Article : Google Scholar : PubMed/NCBI

65 

Fukuda Y, Pazyra-Murphy MF, Silagi ES, Tasdemir-Yilmaz OE, Li Y, Rose L, Yeoh ZC, Vangos NE, Geffken EA, Seo HS, et al: Binding and transport of SFPQ-RNA granules by KIF5A/KLC1 motors promotes axon survival. J Cell Biol. 220:e2020050512021. View Article : Google Scholar : PubMed/NCBI

66 

Mitobe Y, Iino K, Takayama KI, Ikeda K, Suzuki T, Aogi K, Kawabata H, Suzuki Y, Horie-Inoue K and Inoue S: PSF promotes ER-positive breast cancer progression via posttranscriptional regulation of ESR1 and SCFD2. Cancer Res. 80:2230–2242. 2020. View Article : Google Scholar : PubMed/NCBI

67 

Yang X and Wu H: RAS signaling in carcinogenesis, cancer therapy and resistance mechanisms. J Hematol Oncol. 17:1082024. View Article : Google Scholar : PubMed/NCBI

68 

Zhang F, Virshup DM and Cheong JK: Oncogenic RAS-induced CK1α drives nuclear FOXO proteolysis. Oncogene. 37:363–376. 2018. View Article : Google Scholar : PubMed/NCBI

69 

Zhao M, Mishra L and Deng CX: The role of TGF-β/SMAD4 signaling in cancer. Int J Biol Sci. 14:111–123. 2018. View Article : Google Scholar : PubMed/NCBI

70 

Zhang H, Su X, Burley SK and Zheng XFS: mTOR regulates aerobic glycolysis through NEAT1 and nuclear paraspeckle-mediated mechanism in hepatocellular carcinoma. Theranostics. 12:3518–3533. 2022. View Article : Google Scholar : PubMed/NCBI

71 

Bi O, Anene CA, Nsengimana J, Shelton M, Roberts W, Newton-Bishop J and Boyne JR: SFPQ promotes an oncogenic transcriptomic state in melanoma. Oncogene. 40:5192–5203. 2021. View Article : Google Scholar : PubMed/NCBI

72 

Wu CF, Tan GH, Ma CC and Li L: The non-coding RNA llme23 drives the malignant property of human melanoma cells. J Genet Genomics. 40:179–188. 2013. View Article : Google Scholar : PubMed/NCBI

73 

Zheng LQ, Chi SM and Li CX: Rab23′s genetic structure, function and related diseases: A review. Biosci Rep. 37:BSR201604102017. View Article : Google Scholar : PubMed/NCBI

74 

Yasuhara T, Xing YH, Bauer NC, Lee L, Dong R, Yadav T, Soberman RJ, Rivera MN and Zou L: Condensates induced by transcription inhibition localize active chromatin to nucleoli. Mol Cell. 82:2738–2753.e6. 2022. View Article : Google Scholar : PubMed/NCBI

75 

Klotz-Noack K, Klinger B, Rivera M, Bublitz N, Uhlitz F, Riemer P, Lüthen M, Sell T, Kasack K, Gastl B, et al: SFPQ depletion is synthetically Lethal with BRAF(V600E) in colorectal cancer cells. Cell Rep. 32:1081842020. View Article : Google Scholar : PubMed/NCBI

76 

Heinemann V, Douillard JY, Ducreux M and Peeters M: Targeted therapy in metastatic colorectal cancer-an example of personalised medicine in action. Cancer Treat Rev. 39:592–601. 2013. View Article : Google Scholar : PubMed/NCBI

77 

Cancer Genome Atlas Network, . Comprehensive molecular characterization of human colon and rectal cancer. Nature. 487:330–337. 2012. View Article : Google Scholar : PubMed/NCBI

78 

Yaeger R and Corcoran RB: Targeting alterations in the RAF-MEK pathway. Cancer Discov. 9:329–341. 2019. View Article : Google Scholar : PubMed/NCBI

79 

Khamidullina AI, Abramenko YE, Bruter AV and Tatarskiy VV: Key proteins of replication stress response and cell cycle control as cancer therapy targets. Int J Mol Sci. 25:12632024. View Article : Google Scholar : PubMed/NCBI

80 

Takayama KI: Splicing factors have an essential role in prostate cancer progression and androgen receptor signaling. Biomolecules. 9:1312019. View Article : Google Scholar : PubMed/NCBI

81 

Takayama KI, Suzuki T, Fujimura T, Yamada Y, Takahashi S, Homma Y, Suzuki Y and Inoue S: Dysregulation of spliceosome gene expression in advanced prostate cancer by RNA-binding protein PSF. Proc Natl Acad Sci USA. 114:10461–10466. 2017. View Article : Google Scholar : PubMed/NCBI

82 

Jayson GC, Kohn EC, Kitchener HC and Ledermann JA: Ovarian cancer. Lancet. 384:1376–1388. 2014. View Article : Google Scholar : PubMed/NCBI

83 

Pellarin I, Dall'Acqua A, Gambelli A, Pellizzari I, D'Andrea S, Sonego M, Lorenzon I, Schiappacassi M, Belletti B and Baldassarre G: Splicing factor proline- and glutamine-rich (SFPQ) protein regulates platinum response in ovarian cancer-modulating SRSF2 activity. Oncogene. 39:4390–4403. 2020. View Article : Google Scholar : PubMed/NCBI

84 

Sun S, Gao T, Pang B, Su X, Guo C, Zhang R and Pang Q: RNA binding protein NKAP protects glioblastoma cells from ferroptosis by promoting SLC7A11 mRNA splicing in an m(6)A-dependent manner. Cell Death Dis. 13:732022. View Article : Google Scholar : PubMed/NCBI

85 

de Silva HC, Lin MZ, Phillips L, Martin JL and Baxter RC: IGFBP-3 interacts with NONO and SFPQ in PARP-dependent DNA damage repair in triple-negative breast cancer. Cell Mol Life Sci. 76:2015–2030. 2019. View Article : Google Scholar : PubMed/NCBI

86 

Mishchenko TA, Olajide OJ, Gorshkova EN, Vedunova MV and Krysko DV: Regulated cell death modalities: Breaking resistance of temozolomide glioblastoma therapy. Trends Cancer. 11:430–432. 2025. View Article : Google Scholar : PubMed/NCBI

87 

Sun N, Chen Q, Chen H, Sun P, Liu Y, Song D, Yu D, Wang P, Song Y, Qin J, et al: A novel nuclear RNA HSD52 scaffolding NONO/SFPQ complex modulates DNA damage repair to facilitate temozolomide resistance. Neuro Oncol. 27:963–978. 2025. View Article : Google Scholar : PubMed/NCBI

88 

Wang Y and Chen LL: Organization and function of paraspeckles. Essays Biochem. 64:875–882. 2020. View Article : Google Scholar : PubMed/NCBI

89 

Wang Z, Li K and Huang W: Long non-coding RNA NEAT1-centric gene regulation. Cell Mol Life Sci. 77:3769–3779. 2020. View Article : Google Scholar : PubMed/NCBI

90 

Fox AH, Lam YW, Leung AK, Lyon CE, Andersen J, Mann M and Lamond AI: Paraspeckles: A novel nuclear domain. Curr Biol. 12:13–25. 2002. View Article : Google Scholar : PubMed/NCBI

91 

Naganuma T, Nakagawa S, Tanigawa A, Sasaki YF, Goshima N and Hirose T: Alternative 3′-end processing of long noncoding RNA initiates construction of nuclear paraspeckles. EMBO J. 31:4020–4034. 2012. View Article : Google Scholar : PubMed/NCBI

92 

Knott GJ, Bond CS and Fox AH: The DBHS proteins SFPQ, NONO and PSPC1: A multipurpose molecular scaffold. Nucleic Acids Res. 44:3989–4004. 2016. View Article : Google Scholar : PubMed/NCBI

93 

An H, Tan JT and Shelkovnikova TA: Stress granules regulate stress-induced paraspeckle assembly. J Cell Biol. 218:4127–4140. 2019. View Article : Google Scholar : PubMed/NCBI

94 

McCluggage F and Fox AH: Paraspeckle nuclear condensates: Global sensors of cell stress? Bioessays. 43:e20002452021. View Article : Google Scholar : PubMed/NCBI

95 

Pisani G and Baron B: NEAT1 and paraspeckles in cancer development and chemoresistance. Noncoding RNA. 6:432020.PubMed/NCBI

96 

Zhu Y, Hu H, Yuan Z, Zhang Q, Xiong H, Hu Z, Wu H, Huang R, Wang G and Tang Q: LncRNA NEAT1 remodels chromatin to promote the 5-Fu resistance by maintaining colorectal cancer stemness. Cell Death Dis. 11:9622020. View Article : Google Scholar : PubMed/NCBI

97 

Reavie L, Buckley SM, Loizou E, Takeishi S, Aranda-Orgilles B, Ndiaye-Lobry D, Abdel-Wahab O, Ibrahim S, Nakayama KI and Aifantis I: Regulation of c-Myc ubiquitination controls chronic myelogenous leukemia initiation and progression. Cancer Cell. 23:362–375. 2013. View Article : Google Scholar : PubMed/NCBI

98 

Zeng C, Liu S, Lu S, Yu X, Lai J, Wu Y, Chen S, Wang L, Yu Z, Luo G and Li Y: The c-Myc-regulated lncRNA NEAT1 and paraspeckles modulate imatinib-induced apoptosis in CML cells. Mol Cancer. 17:1302018. View Article : Google Scholar : PubMed/NCBI

99 

Bhattacharya A, Wang K, Penailillo J, Chan CN, Fushimi A, Yamashita N, Daimon T, Haratake N, Ozawa H, Nakashoji A, et al: MUC1-C regulates NEAT1 lncRNA expression and paraspeckle formation in cancer progression. Oncogene. 43:2199–2214. 2024. View Article : Google Scholar : PubMed/NCBI

100 

Yang L, Fang C, Zhang R and Zhou S: Prognostic value of oxidative stress-related genes in colorectal cancer and its correlation with tumor immunity. BMC Genomics. 25:82024. View Article : Google Scholar : PubMed/NCBI

101 

Torres S, García-Palmero I, Marín-Vicente C, Bartolomé RA, Calviño E, Fernández-Aceñero MJ and Casal JI: Proteomic characterization of transcription and splicing factors associated with a metastatic phenotype in colorectal cancer. J Proteome Res. 17:252–264. 2018. View Article : Google Scholar : PubMed/NCBI

102 

Zhang D, Yang S, Li Y, Yao J, Ruan J, Zheng Y, Deng Y, Li N, Wei B, Wu Y, et al: Prediction of overall survival among female patients with breast cancer using a prognostic signature based on 8 DNA repair-related genes. JAMA Netw Open. 3:e20146222020. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhang S, Li Z and Fu L: Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review). Mol Med Rep 34: 186, 2026.
APA
Zhang, S., Li, Z., & Fu, L. (2026). Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review). Molecular Medicine Reports, 34, 186. https://doi.org/10.3892/mmr.2026.13896
MLA
Zhang, S., Li, Z., Fu, L."Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review)". Molecular Medicine Reports 34.1 (2026): 186.
Chicago
Zhang, S., Li, Z., Fu, L."Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review)". Molecular Medicine Reports 34, no. 1 (2026): 186. https://doi.org/10.3892/mmr.2026.13896
Copy and paste a formatted citation
x
Spandidos Publications style
Zhang S, Li Z and Fu L: Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review). Mol Med Rep 34: 186, 2026.
APA
Zhang, S., Li, Z., & Fu, L. (2026). Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review). Molecular Medicine Reports, 34, 186. https://doi.org/10.3892/mmr.2026.13896
MLA
Zhang, S., Li, Z., Fu, L."Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review)". Molecular Medicine Reports 34.1 (2026): 186.
Chicago
Zhang, S., Li, Z., Fu, L."Multifaceted regulatory role of proline‑ and glutamine-rich splicing factor in tumors (Review)". Molecular Medicine Reports 34, no. 1 (2026): 186. https://doi.org/10.3892/mmr.2026.13896
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team