Long non‑coding RNA Unigene56159 promotes glioblastoma multiforme cell proliferation and invasion through
negatively regulating microRNA‑194‑5p

Jiang,Guangyu; Dong,Hang; Dong,Yu; Yang,Xinyu

doi:10.3892/mmr.2019.10852

Long non‑coding RNA Unigene56159 promotes glioblastoma multiforme cell proliferation and invasion through negatively regulating microRNA‑194‑5p

Authors:
- Guangyu Jiang
- Hang Dong
- Yu Dong
- Xinyu Yang
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Affiliations: Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Hematology, Shenzhen Seventh People's Hospital/Shenzhen Yantian District People's Hospital (Group), Shenzhen, Guangdong 518109, P.R. China, Department of Neurosurgery, Shenzhen SAMII Medical Center, Shenzhen, Guangdong 518118, P.R. China
Published online on: November 26, 2019 https://doi.org/10.3892/mmr.2019.10852
Pages: 768-776
Copyright : © Jiang et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY 4.0].

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Abstract

Long non‑coding RNAs (lncRNA) serve a vital role in tumor progression. The present study identified a fundamental role for a novel lincRNA, Unigene56159, in the progression of glioblastoma (GBM). Unigene56159 gene expression was found to be significantly upregulated in tissue samples from patients with GBM as well as in GBM cell lines by reverse transcription‑quantitative PCR, while microRNA (miR)‑194‑5p expression levels were decreased. This higher expression level of Unigene56159 was positively correlated with poor overall survival in patients with GBM. However, the mechanism by which this occurs remains to be elucidated. lncRNAs may act as endogenous miRNA sponges for binding to miRNAs or participating in the competitive endogenous RNAs (ceRNA) regulatory network. Small interfering RNA (siRNA) was used to silence the expression of Unigene56159 and inhibit the proliferation and invasion of GBM cell lines by MTT and Transwell assay. Unigene56159 was found to directly interact with miR‑194‑5p, and rescue assay was performed to further confirm that Unigene56159 contributed to glioma progression by regulating miR‑194‑5p. Thus, Unigene56159 may function as a competing endogenous RNA by sequestering miR‑194‑5p in GBM cells. These findings suggested that Unigene56159 may serve an oncogenic role in GBM and may promote disease progression through interacting with miR‑194‑5p. This could be a potential therapeutic target for the treatment of GBM.

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1	Lai NS, Wu DG, Fang XG, Lin YC, Chen SS, Li ZB and Xu SS: Serum microRNA-210 as a potential noninvasive biomarker for the diagnosis and prognosis of glioma. Br J Cancer. 112:1241–1246. 2015. View Article : Google Scholar : PubMed/NCBI
2	Chow KK, Naik S, Kakarla S, Brawley VS, Shaffer DR, Yi Z, Rainusso N, Wu MF, Liu H, Kew Y, et al: T cells redirected to EphA2 for the immunotherapy of glioblastoma. Mol Ther. 21:629–637. 2013. View Article : Google Scholar : PubMed/NCBI
3	Wang K, Kievit FM, Jeon M, Silber JR, Ellenbogen RG and Zhang M: Nanoparticle-mediated target delivery of TRAIL as gene therapy for glioblastoma. Adv Healthc Mater. 4:2719–2726. 2015. View Article : Google Scholar : PubMed/NCBI
4	Delfino KR, Serão NV, Southey BR and Rodriguez-Zas SL: Therapy-, gender- and race-specific microRNA markers, target genes and networks related to glioblastoma recurrence and survival. Cancer Genomics Proteomics. 8:173–183. 2011.PubMed/NCBI
5	Koekkoek JA, Postma TJ, Heimans JJ, Reijneveld JC and Taphoorn MJ: Antiepileptic drug treatment in the end-of-life phase of glioma patients: A feasibility study. Support Care Cancer. 24:1633–1638. 2016. View Article : Google Scholar : PubMed/NCBI
6	Wang J, Su HK, Zhao HF, Chen ZP and To SS: Progress in the application of molecular biomarkers in gliomas. Biochem Biophys Res Commun. 465:1–4. 2015. View Article : Google Scholar : PubMed/NCBI
7	Delgado-López PD and Corrales-García EM: Survival in glioblastoma: A review on the treatment modalities. Clin Transl Oncol. 18:1062–1071. 2016. View Article : Google Scholar : PubMed/NCBI
8	Li C, Jing H, Ma G and Liang P: Allicin induces apoptosis through activation of both intrinsic and extrinsic pathways in glioma cells. Mol Med Rep. 17:5976–5981. 2018.PubMed/NCBI
9	Mrugala MM: Advances and challenges in the treatment of glioblastoma: A clinician's perspective. Discov Med. 83:221–230. 2013.
10	Maruyama R and Suzuki H: Long noncoding RNA involvement in cancer. BMB Rep. 45:604–611. 2012. View Article : Google Scholar : PubMed/NCBI
11	Spizzo R, Almeida MI, Colombatti A and Calin GA: Long non-coding RNAs and cancer: A new frontier of translational research. Oncogene. 31:4577–4587. 2012. View Article : Google Scholar : PubMed/NCBI
12	Grzmil M, Morin P Jr, Lino MM, Merlo A, Frank S, Wang Y, Moncayo G and Hemmings BA: MAP kinase-interacting kinase 1 regulates SMAD2- dependent TGF-β signaling pathway in human glioblastoma. Cancer Res. 71:2392–2402. 2011. View Article : Google Scholar : PubMed/NCBI
13	Zhang S, Wang W, Liu G, Xie S, Li Q, Li Y and Lin Z: Long non-coding RNA HOTTIP promotes hypoxia-induced epithelial-mesenchymal transition of malignant glioma by regulating the miR-101/ZEB1 axis. Biomed Pharmacother. 95:711–720. 2017. View Article : Google Scholar : PubMed/NCBI
14	Zeng J, Du T, Song Y, Gao Y, Li F, Wu R, Chen Y, Li W, Zhou H, Yang Y and Pei Z: Knockdown of long noncoding RNA CCAT2 inhibits cellular proliferation, invasion, and EMT in glioma cells. Oncol Res. 6:913–921. 2017. View Article : Google Scholar
15	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
16	Sullivan TB, Robert LC, Teebagy PA, Morgan SE, Beatty EW, Cicuto BJ, Nowd PK, Rieger-Christ KM and Bryan DJ: Spatiotemporal microRNA profile in peripheral nerve regeneration: miR-138 targets vimentin and inhibits schwann cell migration and proliferation. Neural Regen Res. 13:1253–1262. 2018. View Article : Google Scholar : PubMed/NCBI
17	Tay Y, Kats L, Salmena L, Weiss D, Tan SM, Ala U, Karreth F, Poliseno L, Provero P, Di Cunto F, et al: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs. Cell. 2:344–357. 2011. View Article : Google Scholar
18	Lv J, Fan HX, Zhao XP, Lv P, Fan JY, Zhang Y, Liu M and Tang H: Long non-coding RNA unigene56159 promotes epithelial-mesenchymal transition by acting as a ceRNA of miR-140-5p in hepatocellular carcinoma cells. Cancer Lett. 2:166–175. 2016. View Article : Google Scholar
19	Zhang Z, Lei B, Wu H, Zhang X and Zheng N: Tumor suppressive role of miR-194-5p in glioblastoma multiform. Mol Med Rep. 6:9317–9322. 2017. View Article : Google Scholar
20	Wang Y, Yang L, Chen T, Liu X, Guo Y, Zhu Q, Tong X, Yang W, Xu Q, Huang D and Tu K: A novel lncRNA MCM3AP-AS1 promotes the growth of hepatocellular carcinoma by targeting miR-194-5p/FOXA1 axis. Mol Cancer. 1:282019. View Article : Google Scholar
21	Dell'Aversana C, Giorgio C, D'Amato L, Lania G, Matarese F, Saeed S, Di Costanzo A, Belsito Petrizzi V, Ingenito C, Martens JHA, et al: MiR-194-5p/BCLAF1 deregulation in AML tumorigenesis. Leukemia. 11:2315–2325. 2017. View Article : Google Scholar
22	Zhang Q, Wei T, Shim K, Wright K, Xu K, Palka-Hamblin HL, Jurkevich A and Khare S: Atypical role of sprouty in colorectal cancer: Sprouty repression inhibits epithelial-mesenchymal transition. Oncogene. 24:3151–3162. 2016. View Article : Google Scholar
23	Meng Z, Fu X, Chen X, Zeng S, Tian Y, Jove R, Xu R and Huang W: MiR-194 is a marker of hepatic epithelial cells and suppresses metastasis of liver cancer cells in mice. Hepatology. 6:2148–2157. 2010. View Article : Google Scholar
24	Huang Da W, Sherman BT and Lempicki RA: Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 4:44–57. 2009. View Article : Google Scholar : PubMed/NCBI
25	Robinson MD, Mccarthy DJ and Smyth GK: edgeR: A bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics. 1:139–140. 2010. View Article : Google Scholar
26	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
27	Benjamini Y and Hochberg Y: Controlling the false discovery rate - A practical and powerful approach to multiple testing. J R Stat Soc. 1:289–300. 1995.
28	Egeblad M and Werb Z: New functions for the matrix metalloproteinases in cancer progression. Nat Rev Cancer. 3:161–174. 2002. View Article : Google Scholar
29	Mayer A, Takimoto M, Fritz E, Schellander G, Kofler K and Ludwig H: The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor, and mdr gene expression in colorectal cancer. Cancer. 8:2454–2460. 2015.
30	Gibb EA, Brown CJ and Lam WL: The functional role of long non-coding RNA in human carcinomas. Mol Cancer. 10:382011. View Article : Google Scholar : PubMed/NCBI
31	Qi X, Zhang DH, Wu N, Xiao JH, Wang X and Ma W: CeRNA in cancer: Possible functions and clinical implications. J Med Genet. 10:710–718. 2015. View Article : Google Scholar
32	Tang J, Li Y, Sang Y, Yu B, Lv D, Zhang W and Feng H: LncRNA PVT1 regulates triple-negative breast cancer through KLF5/beta-catenin signaling. Oncogene. 34:4723–4734. 2018. View Article : Google Scholar
33	Sun J, Zhang S, Liu Y, Shan B, Zheng D and Shi J: The lncRNA SNHG5/miR-32 axis regulates gastric cancer cell proliferation and migration by targeting KLF4. FASEB J. 31:893–903. 2017. View Article : Google Scholar : PubMed/NCBI
34	Cui Y, Zhang F, Zhu C, Geng L, Tian T and Liu H: Upregulated lncRNA SNHG1 contributes to progression of non-small cell lung cancer through inhibition of miR-101-3p and activation of Wnt/β-catenin signaling pathway. Oncotarget. 8:17785–17794. 2017.PubMed/NCBI
35	Lu W, Zhang H, Niu Y, Wu Y, Sun W, Li H, Kong J, Ding K, Shen HM, Wu H, et al: Long non-coding RNA linc00673 regulated non-small cell lung cancer proliferation, migration, invasion and epithelial mesenchymal transition by sponging miR-150-5p. Mol Cancer. 16:1182017. View Article : Google Scholar : PubMed/NCBI
36	Cesana M, Cacchiarelli D, Legnini I, Santini T, Sthandier O, Chinappi M, Tramontano A and Bozzoni I: A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA. Cell. 147:358–369. 2011. View Article : Google Scholar : PubMed/NCBI
37	Karreth FA, Tay Y, Perna D, Ala U, Tan SM, Rust AG, DeNicola G, Webster KA, Weiss D, Perez-Mancera PA, et al: In vivo identification of tumor- suppressive PTEN ceRNAs in an oncogenic BRAF-induced mouse model of melanoma. Cell. 147:382–395. 2011. View Article : Google Scholar : PubMed/NCBI