LINC01116 promotes the proliferation and invasion of glioma by regulating the microRNA‑744‑5p‑MDM2‑p53 axis

Jiang,Li; Cheng,Chao; Ji,Wei; Wang,Hao; Du,Quan; Dong,Xiaoqiao; Shao,Junfei; Yu,Wenhua

doi:10.3892/mmr.2021.12005

LINC01116 promotes the proliferation and invasion of glioma by regulating the microRNA‑744‑5p‑MDM2‑p53 axis

Authors:
- Li Jiang
- Chao Cheng
- Wei Ji
- Hao Wang
- Quan Du
- Xiaoqiao Dong
- Junfei Shao
- Wenhua Yu
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Affiliations: Department of Neurosurgery, Hangzhou First People's Hospital of Nanjing Medical University, Hangzhou, Zhejiang 310006, P.R. China, Department of Neurosurgery, Wuxi People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214023, P.R. China
Published online on: March 16, 2021 https://doi.org/10.3892/mmr.2021.12005
Article Number: 366
Copyright: © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Long non‑coding RNAs (lncRNAs) have been implicated in the development and progression of tumors. However, the roles and underlying mechanisms of long intergenic non‑protein coding RNA 1116 (LINC01116), a member of the lncRNA family, in glioma progression are largely unclear. The expression of LINC01116 and microRNA (miR)‑744‑5p in glioma tissues and cells was detected by reverse transcription‑quantitative PCR. The influences of LINC01116 or miR‑744‑5p on cell proliferation and invasion were evaluated by Cell Counting Kit‑8, colony formation and Transwell assays, and western blotting was used to detect the expression of p53 pathway proteins. A dual‑luciferase reporter system was used to locate common binding sites between miR‑744‑5p and LINC01116 or the 3' untranslated region of E3 ubiquitin‑protein ligase Mdm2 (MDM2). RNA immunoprecipitation was used to determine the interactions between RNAs and proteins. Moreover, a xenograft mouse model was constructed to investigate the effects of LINC01116 in vivo, followed by a TdT‑mediated dUTP nick end labeling assay to determine the degree of apoptosis in nude mouse tumors. LINC01116 was found to be highly expressed in glioma tissues, which was associated with a malignant phenotype. LINC01116 promoted the proliferation and invasiveness of glioma cells, and inhibited the p53 pathway by preserving the expression of MDM2 mRNA via miR‑744‑5p sponging. Furthermore, a low degree of miR‑744‑5p expression was observed in glioma tissues, which was negatively associated with the expression of LINC01116. Overexpression of miR‑744‑5p inhibited the proliferation and invasiveness of glioma cells, which was rescued by LINC01116. Finally, LINC01116 knockdown inhibited tumor growth in nude mice. In conclusion, LINC01116 is aberrantly expressed and promotes the progression of glioma by regulating the miR‑744‑5p‑MDM2‑p53 pathway. In future, targeting LINC01116 may therefore be a potential therapeutic approach for patients with glioma.

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1	Gusyatiner O and Hegi ME: Glioma epigenetics: From ubclassification to novel treatment options. Semin Cancer Biol. 51:50–58. 2018. View Article : Google Scholar : PubMed/NCBI
2	Aldape K, Brindle KM, Chesler L, Chopra R, Gajjar A, Gilbert MR, Gottardo N, Gutmann DH, Hargrave D, Holland EC, et al: Challenges to curing primary brain tumours. Nat Rev Clin Oncol. 16:509–520. 2019. View Article : Google Scholar : PubMed/NCBI
3	Lapointe S, Perry A and Butowski NA: Primary brain tumours in adults. Lancet. 392:432–446. 2018. View Article : Google Scholar : PubMed/NCBI
4	Post-transcriptional processing generates a diversity of 5′-modified long and short RNAs. Nature. 457:1028–1032. 2009. View Article : Google Scholar : PubMed/NCBI
5	Arun G, Diermeier SD and Spector DL: Therapeutic targeting of long non-coding RNAs in cancer. Trends Mol Med. 24:257–277. 2018. View Article : Google Scholar : PubMed/NCBI
6	Salmena L, Poliseno L, Tay Y, Kats L and Pandolfi PP: A ceRNA hypothesis: The rosetta stone of a hidden RNA language? Cell. 146:353–358. 2011. View Article : Google Scholar : PubMed/NCBI
7	Qi X, Zhang DH, Wu N, Xiao JH, Wang X and Ma W: ceRNA in cancer: Possible functions and clinical implications. J Med Genet. 52:710–718. 2015. View Article : Google Scholar : PubMed/NCBI
8	Abdollahzadeh R, Daraei A, Mansoori Y, Sepahvand M, Amoli MM and Tavakkoly-Bazzaz J: Competing endogenous RNA (ceRNA) cross talk and language in ceRNA regulatory networks: A new look at hallmarks of breast cancer. J Cell Physiol. 234:10080–10100. 2019. View Article : Google Scholar : PubMed/NCBI
9	Qu S, Liu Z, Yang X, Zhou J, Yu H, Zhang R and Li H: The emerging functions and roles of circular RNAs in cancer. Cancer Lett. 414:301–309. 2018. View Article : Google Scholar : PubMed/NCBI
10	Schmitt AM and Chang HY: Long noncoding RNAs in cancer pathways. Cancer Cell. 29:452–463. 2016. View Article : Google Scholar : PubMed/NCBI
11	Wang KC and Chang HY: Molecular mechanisms of long noncoding RNAs. Mol Cell. 43:904–914. 2011. View Article : Google Scholar : PubMed/NCBI
12	Peng Z, Liu C and Wu M: New insights into long noncoding RNAs and their roles in glioma. Mol Cancer. 17:612018. View Article : Google Scholar : PubMed/NCBI
13	Lin C and Yang L: Long Noncoding RNA in cancer: Wiring signaling circuitry. Trends Cell Biol. 28:287–301. 2018. View Article : Google Scholar : PubMed/NCBI
14	Kopp F and Mendell JT: Functional classification and experimental dissection of long noncoding RNAs. Cell. 172:393–407. 2018. View Article : Google Scholar : PubMed/NCBI
15	Tang Z, Li C, Kang B, Gao G and Zhang Z: GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res. 45:W98–W102. 2017. View Article : Google Scholar : PubMed/NCBI
16	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
17	Li JH, Liu S, Zhou H, Qu LH and Yang JH: StarBase v2.0: Decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interaction networks from large-scale CLIP-Seq data. Nucleic Acids Res. 42:D92–D97. 2014. View Article : Google Scholar : PubMed/NCBI
18	Peters L and Meister G: Argonaute proteins: Mediators of RNA silencing. Mol Cell. 26:611–623. 2007. View Article : Google Scholar : PubMed/NCBI
19	Filipowicz W, Bhattacharyya SN and Sonenberg N: Mechanisms of post-transcriptional regulation by microRNAs: Are the answers in sight? Nat Rev Genet. 9:102–114. 2008. View Article : Google Scholar : PubMed/NCBI
20	National Research Council: Guide for the Care and Use of Laboratory Animals. The National Academies Press; Washington, DC: 1996
21	Alavi MV: Targeted OMA1 therapies for cancer. Int J Cancer. 145:2330–2341. 2019. View Article : Google Scholar : PubMed/NCBI
22	Thu HE, Hussain Z, Mohamed IN and Shuid AN: Eurycoma longifolia, a potential phytomedicine for the treatment of cancer: Evidence of p53-mediated apoptosis in cancerous cells. Curr Drug Targets. 19:1109–1126. 2018. View Article : Google Scholar : PubMed/NCBI
23	Jung E, Alfonso J, Osswald M, Monyer H, Wick W and Winkler F: Emerging intersections between neuroscience and glioma biology. Nat Neurosci. 22:1951–1960. 2019. View Article : Google Scholar : PubMed/NCBI
24	Rynkeviciene R, Simiene J, Strainiene E, Stankevicius V, Usinskiene J, Kaubriene EM, Meskinyte I, Cicenas J and Suziedelis K: Non-coding RNAs in glioma. Cancers (Basel). 11:172018. View Article : Google Scholar
25	Zheng Y, Xie J, Xu X, Yang X, Zhou Y, Yao Q and Xiong Y: lncRNA DDX11-AS1 exerts oncogenic roles in glioma through regulating miR-499b-5p/RWDD4 axis. Onco Targets Ther. 14:157–164. 2021. View Article : Google Scholar : PubMed/NCBI
26	Wei Y, Zhou K, Wang C, Du X, Xiao Q and Chen C: Adsorption of miR-218 by lncRNA HOTAIR regulates PDE7A and affects glioma cell proliferation, invasion, and apoptosis. Int J Clin Exp Pathol. 13:2973–2983. 2020.PubMed/NCBI
27	Wu YJ, Yang QS, Chen H, Wang JT, Wang WB and Zhou L: Long non-coding RNA CASC19 promotes glioma progression by modulating the miR-454-3p/RAB5A axis and is associated with unfavorable MRI features. Oncol Rep. 45:728–737. 2021. View Article : Google Scholar
28	Wang H, Lu B, Ren S, Wu F, Wang X, Yan C and Wang Z: Long noncoding RNA LINC01116 contributes to gefitinib resistance in non-small cell lung cancer through regulating IFI44. Mol Ther Nucleic Acids. 19:218–227. 2020. View Article : Google Scholar : PubMed/NCBI
29	Hu HB, Chen Q and Ding SQ: lncRNA LINC01116 competes with miR-145 for the regulation of ESR1 expression in breast cancer. Eur Rev Med Pharmacol Sci. 22:1987–1993. 2018.PubMed/NCBI
30	Chen J, Yuan ZH, Hou XH, Shi MH and Jiang R: LINC01116 promotes the proliferation and inhibits the apoptosis of gastric cancer cells. Eur Rev Med Pharmacol Sci. 24:1807–1814. 2020.PubMed/NCBI
31	Xing H, Sun H and Du W: LINC01116 accelerates nasopharyngeal carcinoma progression based on its enhancement on MYC transcription activity. Cancer Med. 9:267–277. 2020. View Article : Google Scholar
32	Zhang ZF, Xu HH, Hu WH, Hu TY and Wang XB: LINC01116 promotes proliferation, invasion and migration of osteosarcoma cells by silencing p53 and EZH2. Eur Rev Med Pharmacol Sci. 23:6813–6823. 2019.PubMed/NCBI
33	Wu J, Chen Z, Zhang L, Cao J, Li X, Gong Z, Bo H, Zhang S and He D: Knockdown of LINC01116 inhibits cell migration and invasion in head and neck squamous cell carcinoma through epithelial-mesenchymal transition pathway. J Cell Biochem. 121:867–875. 2020. View Article : Google Scholar : PubMed/NCBI
34	Chen Z, Tao Q, Qiao B and Zhang L: Silencing of LINC01116 suppresses the development of oral squamous cell carcinoma by up-regulating microRNA-136 to inhibit FN1. Cancer Manag Res. 11:6043–6059. 2019. View Article : Google Scholar : PubMed/NCBI
35	Ye J, Zhu J, Chen H, Qian J, Zhang L, Wan Z, Chen F, Sun S, Li W and Luo C: A novel lncRNA-LINC01116 regulates tumorigenesis of glioma by targeting VEGFA. Int J Cancer. 146:248–261. 2020. View Article : Google Scholar : PubMed/NCBI
36	Fang YN, Huang ZL, Li H, Tan WB, Zhang QG, Wang L and Wu JL: LINC01116 promotes the progression of epithelial ovarian cancer via regulating cell apoptosis. Eur Rev Med Pharmacol Sci. 22:5127–5133. 2018.PubMed/NCBI
37	Zhang B, Yu L, Han N, Hu Z, Wang S, Ding L and Jiang J: LINC01116 targets miR-520a-3p and affects IL6R to promote the proliferation and migration of osteosarcoma cells through the Jak-stat signaling pathway. Biomed Pharmacother. 107:270–282. 2018. View Article : Google Scholar : PubMed/NCBI
38	Wade M, Li YC and Wahl GM: MDM2, MDMX and p53 in oncogenesis and cancer therapy. Nat Rev Cancer. 13:83–96. 2013. View Article : Google Scholar : PubMed/NCBI
39	Tiwari B, Jones AE and Abrams JM: Transposons, p53 and genome security. Trends Genet. 34:846–855. 2018. View Article : Google Scholar : PubMed/NCBI
40	Hafner A, Bulyk ML, Jambhekar A and Lahav G: The multiple mechanisms that regulate p53 activity and cell fate. Nat Rev Mol Cell Biol. 20:199–210. 2019. View Article : Google Scholar : PubMed/NCBI
41	Stiewe T and Haran TE: How mutations shape p53 interactions with the genome to promote tumorigenesis and drug resistance. Drug Resist Updat. 38:27–43. 2018. View Article : Google Scholar : PubMed/NCBI
42	Oliner JD, Saiki AY and Caenepeel S: The role of MDM2 amplification and overexpression in tumorigenesis. Cold Spring Harb Perspect Med. 6:a0263362016. View Article : Google Scholar : PubMed/NCBI
43	Wu X, Bayle JH, Olson D and Levine AJ: The p53-mdm-2 autoregulatory feedback loop. Genes Dev. 7:1126–1132. 1993. View Article : Google Scholar : PubMed/NCBI
44	Hernandez-Monge J, Rousset-Roman AB, Medina-Medina I and Olivares-Illana V: Dual function of MDM2 and MDMX toward the tumor suppressors p53 and RB. Genes Cancer. 7:278–287. 2016. View Article : Google Scholar : PubMed/NCBI
45	Zhao J, Li L, Han ZY, Wang ZX and Qin LX: Long noncoding RNAs, emerging and versatile regulators of tumor-induced angiogenesis. Am J Cancer Res. 9:1367–1381. 2019.PubMed/NCBI
46	Adams BD, Parsons C, Walker L, Zhang WC and Slack FJ: Targeting noncoding RNAs in disease. J Clin Invest. 127:761–771. 2017. View Article : Google Scholar : PubMed/NCBI
47	Bracken CP, Scott HS and Goodall GJ: A network-biology perspective of microRNA function and dysfunction in cancer. Nat Rev Genet. 17:719–732. 2016. View Article : Google Scholar : PubMed/NCBI
48	Anfossi S, Babayan A, Pantel K and Calin GA: Clinical utility of circulating non-coding RNAs - an update. Nat Rev Clin Oncol. 15:541–563. 2018. View Article : Google Scholar : PubMed/NCBI