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
November-2017 Volume 16 Issue 5

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
November-2017 Volume 16 Issue 5

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
Article Open Access

Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing

  • Authors:
    • Yao Liu
    • Zhe Yang
    • Feng Du
    • Qiao Yang
    • Jie Hou
    • Xiaohong Yan
    • Yi Geng
    • Yaning Zhao
    • Hua Wang
  • View Affiliations / Copyright

    Affiliations: Department of Infectious Diseases, Baoji Municipal Central Hospital, Baoji, Shaanxi 721008, P.R. China
    Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 6674-6682
    |
    Published online on: September 11, 2017
       https://doi.org/10.3892/mmr.2017.7457
  • 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

The present study aimed to explore the underlying molecular mechanisms of hepatocellular carcinoma (HCC). RNA‑sequencing profiles GSM629264 and GSM629265, from the GSE25599 data set, were downloaded from the Gene Expression Omnibus database and processed by quality evaluation. GSM629264 and GSM629265 were from HCC and adjacent non‑cancerous tissues, respectively. TopHat software was used for alignment analysis, followed by the detection of novel splicing sites. In addition, the Cufflinks software package was used to analyze gene expressions, and the Cuffdiff program was used to screen for differently expressed genes (DEGs) and differentially expressed splicing variants. Gene ontology functional enrichment and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses of DEGs were also performed. Transcription factors (TFs) and microRNAs (miRNAs) that regulate DEGs were identified, and a protein‑protein interaction (PPI) network was constructed. The hub node in the PPI network was obtained, and the TFs and miRNAs that regulated the hub node were further predicted. The quality of the sequencing data met the standards for analysis, and the clean reads were ~65%. Most sequencing reads mapped into coding sequence exons (CDS_exons), whereas other reads mapped into exon 3' untranslated regions (UTR_Exons), 5'UTR_Exons and Introns. Upregulated and downregulated DEGs between HCC and adjacent non‑cancerous tissues were screened. Genes of differentially expressed splicing variants were identified, including vesicle‑associated membrane protein 4, phosphatidylinositol glycan anchor biosynthesis class C, protein disulfide isomerase family A member 4 and growth arrest specific 5. Screened DEGs were enriched in the complement pathway. In the PPI network, ubiquitin C (UBC) was the hub node. UBC was predicted to be regulated by several TFs, including specificity protein 1 (SP1), FBJ murine osteosarcoma viral oncogene homolog (FOS), proto‑oncogene c‑JUN (JUN), FOS‑like antigen 2 (FOSL2) and SWI/SNF‑related, matrix‑associated, actin‑dependent regulator of chromatin, subfamily A, member 4 (SMARCA4), and several miRNAs, including miR‑30 and miR‑181. Results from the present study demonstrated that UBC, SP1, FOS, JUN, FOSL2, SMARCA4, miR‑30 and miR‑181 may participate in the development of HCC.
View Figures

Figure 1

Figure 2

Figure 3

View References

1 

Butt Z, Mallick R, Mulcahy MF, Benson AB, Cella D and Kaiser K: Pain and other symptoms in patients with hepatocellular carcinoma (HCC): A qualitative analysis. J. Clin Oncol. 2013.

2 

Hashimoto E and Tokushige K: Prevalence, gender, ethnic variations, and prognosis of NASH. J Gastroenterol. 46 Suppl 1:63–69. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Simonetti J, Bulkow L, McMahon BJ, Homan C, Snowball M, Negus S, Williams J and Livingston SE: Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus. Hepatology. 51:1531–1537. 2010. View Article : Google Scholar : PubMed/NCBI

4 

Schwartz M, Roayaie S and Uva P: Treatment of HCC in patients awaiting liver transplantation. Am J Transplant. 7:1875–1881. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Huang Q, Lin B, Liu H, Ma X, Mo F, Yu W, Li L, Li H, Tian T, Wu D, et al: RNA-Seq analyses generate comprehensive transcriptomic landscape and reveal complex transcript patterns in hepatocellular carcinoma. PLoS One. 6:e261682011. View Article : Google Scholar : PubMed/NCBI

6 

Wong CM, Ng YL, Lee JM, Wong CC, Cheung OF, Chan CY, Tung EK, Ching YP and Ng IO: Tissue factor pathway inhibitor-2 as a frequently silenced tumor suppressor gene in hepatocellular carcinoma. Hepatology. 45:1129–1138. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Chen PJ, Yeh SH, Liu WH, Lin CC, Huang HC, Chen CL, Chen DS and Chen PJ: Androgen pathway stimulates MicroRNA-216a transcription to suppress the tumor suppressor in lung cancer-1 gene in early hepatocarcinogenesis. Hepatology. 56:632–643. 2012. View Article : Google Scholar : PubMed/NCBI

8 

Liu W, Li X, Chu ES, Go MY, Xu L, Zhao G, Li L, Dai N, Si J, Tao Q, et al: Paired box gene 5 is a novel tumor suppressor in hepatocellular carcinoma through interaction with p53 signaling pathway. Hepatology. 53:843–853. 2011. View Article : Google Scholar : PubMed/NCBI

9 

Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, et al: NCBI GEO: Archive for functional genomics data sets-update. Nucleic Acids Res. 41(Database Issue): D991–D995. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Auer PL and Doerge RW: Statistical design and analysis of RNA sequencing data. Genetics. 185:405–416. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Lin LI: A concordance correlation coefficient to evaluate reproducibility. Biometrics. 45:255–268. 1989. View Article : Google Scholar : PubMed/NCBI

12 

Hansen P and Delattre M: Complete-link cluster analysis by graph coloring. J American Statistical Association. 73:397–403. 1978. View Article : Google Scholar

13 

da W Huang, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2008. View Article : Google Scholar

14 

Goldberg DS and Roth FP: Assessing experimentally derived interactions in a small world. Proc Natl Acad Sci USA. 100:4372–4376. 2003; View Article : Google Scholar : PubMed/NCBI

15 

Lam VW, Laurence JM, Johnston E, Hollands MJ, Pleass HC and Richardson AJ: A systematic review of two-stage hepatectomy in patients with initially unresectable colorectal liver metastases. HPB. 15:483–491. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Ockner RK, Kaikaus RM and Bass NM: Fatty-acid metabolism and the pathogenesis of hepatocellular carcinoma: Review and hypothesis. Hepatology. 18:669–676. 1993. View Article : Google Scholar : PubMed/NCBI

17 

Cheng J, Imanishi H, Amuro Y and Hada T: NS-398, a selective cyclooxygenase 2 inhibitor, inhibited cell growth and induced cell cycle arrest in human hepatocellular carcinoma cell lines. Int J Cancer. 99:755–761. 2002. View Article : Google Scholar : PubMed/NCBI

18 

Zhou L, Wang Q, Yin P, Xing W, Wu Z, Chen S, Lu X, Zhang Y, Lin X and Xu G: Serum metabolomics reveals the deregulation of fatty acids metabolism in hepatocellular carcinoma and chronic liver diseases. Anal Bioanal Chem. 403:203–213. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Hochstrasser M: Ubiquitin, proteasomes, and the regulation of intracellular protein degradation. Curr Opin Cell Biol. 7:215–223. 1995. View Article : Google Scholar : PubMed/NCBI

20 

Chan DW, Chan CY, Yam JW, Ching YP and Ng IO: Prickle-1 negatively regulates Wnt/beta-catenin pathway by promoting Dishevelled ubiquitination/degradation in liver cancer. Gastroenterology. 131:1218–1227. 2006. View Article : Google Scholar : PubMed/NCBI

21 

Hoeller D, Hecker CM and Dikic I: Ubiquitin and ubiquitin-like proteins in cancer pathogenesis. Nat Rev Cancer. 6:776–788. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Bertrand MJ, Milutinovic S, Dickson KM, Ho WC, Boudreault A, Durkin J, Gillard JW, Jaquith JB, Morris SJ and Barker PA: cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol Cell. 30:689–700. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Sureban SM, Qu D and Houchen CW: Epigenetic Variations of Stem Cell Markers in CancerEpigenetics and Cancer. Springer; pp. 115–128. 2013, View Article : Google Scholar

24 

Magan N, Szremska AP, Isaacs RJ and Stowell KM: Modulation of DNA topoisomerase II alpha promoter activity by members of the Sp (specificity protein) and NF-Y (nuclear factor Y) families of transcription factors. Biochem J. 374:723–729. 2003. View Article : Google Scholar : PubMed/NCBI

25 

Marin M, Karis A, Visser P, Grosveld F and Philipsen S: Transcription factor Sp1 is essential for early embryonic development but dispensable for cell growth and differentiation. Cell. 89:619–628. 1997. View Article : Google Scholar : PubMed/NCBI

26 

Wang YT, Chuang JY, Shen MR, Yang WB, Chang WC and Hung JJ: Sumoylation of specificity protein 1 augments its degradation by changing the localization and increasing the specificity protein 1 proteolytic process. J Mol Biol. 380:869–885. 2008. View Article : Google Scholar : PubMed/NCBI

27 

Bossis G, Malnou CE, Farras R, Andermarcher E, Hipskind R, Rodriguez M, Schmidt D, Muller S, Jariel-Encontre I and Piechaczyk M: Down-regulation of c-Fos/c-Jun AP-1 dimer activity by sumoylation. Mol Cell Biol. 25:6964–6979. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Min L, Ji Y, Bakiri L, Qiu Z, Cen J, Chen X, Chen L, Scheuch H, Zheng H, Qin L, et al: Liver cancer initiation is controlled by AP-1 through SIRT6-dependent inhibition of survivin. Nat Cell Biol. 14:1203–1211. 2012. View Article : Google Scholar : PubMed/NCBI

29 

Wang Z, Xiang Q, Li D and Li S: Correlation between gene expression and chromatin conformation of c-fos and N-ras in human liver and hepatoma. Chin Med Sci J. 6:6–8. 1991.PubMed/NCBI

30 

Wu C, Gong Y, Yuan J, Zhang W, Zhao G, Li H, Sun A, Kai Hu, Zou Y and Ge J: microRNA-181a represses ox-LDL-stimulated inflammatory response in dendritic cell by targeting c-Fos. J Lipid Res. 53:2355–2363. 2012. View Article : Google Scholar : PubMed/NCBI

31 

Wilson BG and Roberts CW: SWI/SNF nucleosome remodellers and cancer. Nat Rev Cancer. 11:481–492. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Medina PP, Romero OA, Kohno T, Montuenga LM, Pio R, Yokota J and Sanchez-Cespedes M: Frequent BRG1/SMARCA4-inactivating mutations in human lung cancer cell lines. Hum Mutat. 29:617–622. 2008. View Article : Google Scholar : PubMed/NCBI

33 

Ramos P, Karnezis AN, Hendricks WP, Wang Y, Tembe W, Zismann VL, Legendre C, Liang WS, Russell ML, Craig DW, et al: Loss of the tumor suppressor SMARCA4 in small cell carcinoma of the ovary, hypercalcemic type (SCCOHT). Rare Dis. 2:e9671482014. View Article : Google Scholar : PubMed/NCBI

34 

Guichard C, Amaddeo G, Imbeaud S, Ladeiro Y, Pelletier L, Maad IB, Calderaro J, Bioulac-Sage P, Letexier M, Degos F, et al: Integrated analysis of somatic mutations and focal copy-number changes identifies key genes and pathways in hepatocellular carcinoma. Nat Genet. 44:694–698. 2012. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu Y, Yang Z, Du F, Yang Q, Hou J, Yan X, Geng Y, Zhao Y and Wang H: Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing. Mol Med Rep 16: 6674-6682, 2017.
APA
Liu, Y., Yang, Z., Du, F., Yang, Q., Hou, J., Yan, X. ... Wang, H. (2017). Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing. Molecular Medicine Reports, 16, 6674-6682. https://doi.org/10.3892/mmr.2017.7457
MLA
Liu, Y., Yang, Z., Du, F., Yang, Q., Hou, J., Yan, X., Geng, Y., Zhao, Y., Wang, H."Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing". Molecular Medicine Reports 16.5 (2017): 6674-6682.
Chicago
Liu, Y., Yang, Z., Du, F., Yang, Q., Hou, J., Yan, X., Geng, Y., Zhao, Y., Wang, H."Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing". Molecular Medicine Reports 16, no. 5 (2017): 6674-6682. https://doi.org/10.3892/mmr.2017.7457
Copy and paste a formatted citation
x
Spandidos Publications style
Liu Y, Yang Z, Du F, Yang Q, Hou J, Yan X, Geng Y, Zhao Y and Wang H: Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing. Mol Med Rep 16: 6674-6682, 2017.
APA
Liu, Y., Yang, Z., Du, F., Yang, Q., Hou, J., Yan, X. ... Wang, H. (2017). Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing. Molecular Medicine Reports, 16, 6674-6682. https://doi.org/10.3892/mmr.2017.7457
MLA
Liu, Y., Yang, Z., Du, F., Yang, Q., Hou, J., Yan, X., Geng, Y., Zhao, Y., Wang, H."Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing". Molecular Medicine Reports 16.5 (2017): 6674-6682.
Chicago
Liu, Y., Yang, Z., Du, F., Yang, Q., Hou, J., Yan, X., Geng, Y., Zhao, Y., Wang, H."Molecular mechanisms of pathogenesis in hepatocellular carcinoma revealed by RNA‑sequencing". Molecular Medicine Reports 16, no. 5 (2017): 6674-6682. https://doi.org/10.3892/mmr.2017.7457
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