miR-142 inhibits the migration and invasion of glioma by targeting Rac1

Qin,Wenyi; Rong,Xiaofeng; Dong,Jiangchuan; Yu,Chao; Yang,Juan

doi:10.3892/or.2017.5816

miR-142 inhibits the migration and invasion of glioma by targeting Rac1

Authors:
- Wenyi Qin
- Xiaofeng Rong
- Jiangchuan Dong
- Chao Yu
- Juan Yang
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Affiliations: Department of Integrated Chinese and Western Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, P.R. China, Department of Emergency, The Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, P.R. China, Department of Emergency, Chongqing JiangBei Hospital of Traditional Chinese Medicine, Chongqing 400020, P.R. China
Published online on: July 13, 2017 https://doi.org/10.3892/or.2017.5816
Pages: 1543-1550

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Abstract

Increasing evidence has shown that aberrant microRNAs (miRNAs) are implicated in tumorigenesis and tumor progression by regulating oncogenes or tumor suppressors. Dysregulation of miR-142 has been reported in multiple tumors. However, its clinical roles and underlying mechanism in glioma remain to be elucidated. In the present study, we found that the expression of miR-142 was significantly downregulated in both glioma tissues and cell lines by qRT-PCR. Clinical analysis revealed that decreased miR-142 was markedly associated with advanced World Health Organization (WHO) grade. Moreover, we disclosed that miR-142 was a novel independent prognostic marker in the prediction of the 5-year survival of glioma patients. The ectopic overexpression of miR-142 inhibited cell migration, invasion and invasion‑related gene expression. Notably, miR-142 modulated Rac1 by directly binding to its 3'-untranslated (3'-UTR) region, leading to the suppression of the expression of matrix metalloproteinases (MMPs). In glioma clinical samples, miR-142 was inversely correlated with Rac1 expression, and played positive roles in glioma migration and invasion. Alteration of Rac1 expression at least partially abolished the migration, invasion and MMP expression of miR-142 in glioma cells. In the present study, we identified Rac1 as a functional target of miR-142 in glioma. In conclusion, our data indicated that miR-142 inhibited the migration, invasion and MMP expression of glioma by targeting Rac1, and may represent a novel potential therapeutic target and prognostic marker for glioma.

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1	Vredenburgh JJ, Desjardins A, Reardon DA and Friedman HS: Experience with irinotecan for the treatment of malignant glioma. Neuro Oncol. 11:80–91. 2009. View Article : Google Scholar : PubMed/NCBI
2	Xie Q, Mittal S and Berens ME: Targeting adaptive glioblastoma: An overview of proliferation and invasion. Neuro Oncol. 16:1575–1584. 2014. View Article : Google Scholar : PubMed/NCBI
3	Preusser M, Haberler C and Hainfellner JA: Malignant glioma: Neuropathology and neurobiology. Wien Med Wochenschr. 156:332–337. 2006. View Article : Google Scholar : PubMed/NCBI
4	Vigneswaran K, Neill S and Hadjipanayis CG: Beyond the World Health Organization grading of infiltrating gliomas: Advances in the molecular genetics of glioma classification. Ann Transl Med. 3:952015.PubMed/NCBI
5	Cohen AL and Colman H: Glioma biology and molecular markers. Cancer Treat Res. 163:15–30. 2015. View Article : Google Scholar : PubMed/NCBI
6	Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al: European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group: Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 352:987–996. 2005. View Article : Google Scholar : PubMed/NCBI
7	Davis FG and McCarthy BJ: Current epidemiological trends and surveillance issues in brain tumors. Expert Rev Anticancer Ther. 1:395–401. 2001. View Article : Google Scholar : PubMed/NCBI
8	Makeyev EV and Maniatis T: Multilevel regulation of gene expression by microRNAs. Science. 319:1789–1790. 2008. View Article : Google Scholar : PubMed/NCBI
9	Bartels CL and Tsongalis GJ: MicroRNAs: Novel biomarkers for human cancer. Clin Chem. 55:623–631. 2009. View Article : Google Scholar : PubMed/NCBI
10	Esquela-Kerscher A and Slack FJ: Oncomirs - microRNAs with a role in cancer. Nat Rev Cancer. 6:259–269. 2006. View Article : Google Scholar : PubMed/NCBI
11	Liu Z, Dou C, Yao B, Xu M, Ding L, Wang Y, Jia Y, Li Q, Zhang H, Tu K, et al: Methylation-mediated repression of microRNA-129-2 suppresses cell aggressiveness by inhibiting high mobility group box 1 in human hepatocellular carcinoma. Oncotarget. 7:36909–36923. 2016. View Article : Google Scholar : PubMed/NCBI
12	Wu J, Cui H, Zhu Z and Wang L: MicroRNA-200b-3p suppresses epithelial-mesenchymal transition and inhibits tumor growth of glioma through down-regulation of ERK5. Biochem Biophys Res Commun. 478:1158–1164. 2016. View Article : Google Scholar : PubMed/NCBI
13	Deng B, Zhang Y, Zhang S, Wen F, Miao Y and Guo K: MicroRNA-142-3p inhibits cell proliferation and invasion of cervical cancer cells by targeting FZD7. Tumour Biol. 36:8065–8073. 2015. View Article : Google Scholar : PubMed/NCBI
14	Malzkorn B, Wolter M, Liesenberg F, Grzendowski M, Stühler K, Meyer HE and Reifenberger G: Identification and functional characterization of microRNAs involved in the malignant progression of gliomas. Brain Pathol. 20:539–550. 2010. View Article : Google Scholar : PubMed/NCBI
15	Cao XC, Yu Y, Hou LK, Sun XH, Ge J, Zhang B and Wang X: miR-142-3p inhibits cancer cell proliferation by targeting CDC25C. Cell Prolif. 49:58–68. 2016. View Article : Google Scholar : PubMed/NCBI
16	Pan D, Du Y, Ren Z, Chen Y, Li X, Wang J and Hu B: Radiation induces premature chromatid separation via the miR-142-3p/Bod1 pathway in carcinoma cells. Oncotarget. 7:60432–60445. 2016. View Article : Google Scholar : PubMed/NCBI
17	Ma Z, Liu T, Huang W, Liu H, Zhang HM, Li Q, Chen Z and Guo AY: MicroRNA regulatory pathway analysis identifies miR-142-5p as a negative regulator of TGF-β pathway via targeting SMAD3. Oncotarget. 7:71504–71513. 2016.PubMed/NCBI
18	Zheng Z, Ding M, Ni J, Song D, Huang J and Wang J: miR-142 acts as a tumor suppressor in osteosarcoma cell lines by targeting Rac1. Oncol Rep. 33:1291–1299. 2015.PubMed/NCBI
19	Su YH, Zhou Z, Yang KP, Wang XG, Zhu Y and Fa XE: MIR-142-5p and miR-9 may be involved in squamous lung cancer by regulating cell cycle related genes. Eur Rev Med Pharmacol Sci. 17:3213–3220. 2013.PubMed/NCBI
20	Yin Y, Song M, Gu B, Qi X, Hu Y, Feng Y, Liu H, Zhou L, Bian Z, Zhang J, et al: Systematic analysis of key miRNAs and related signaling pathways in colorectal tumorigenesis. Gene. 578:177–184. 2016. View Article : Google Scholar : PubMed/NCBI
21	Shen WW, Zeng Z, Zhu WX and Fu GH: MiR-142-3p functions as a tumor suppressor by targeting CD133, ABCG2, and Lgr5 in colon cancer cells. J Mol Med. 91:989–1000. 2013. View Article : Google Scholar : PubMed/NCBI
22	Xu G, Wang J, Jia Y, Shen F, Han W and Kang Y: MiR-142-3p functions as a potential tumor suppressor in human osteosarcoma by targeting HMGA1. Cell Physiol Biochem. 33:1329–1339. 2014. View Article : Google Scholar : PubMed/NCBI
23	Kaduthanam S, Gade S, Meister M, Brase JC, Johannes M, Dienemann H, Warth A, Schnabel PA, Herth FJ, Sültmann H, et al: Serum miR-142-3p is associated with early relapse in operable lung adenocarcinoma patients. Lung Cancer. 80:223–227. 2013. View Article : Google Scholar : PubMed/NCBI
24	Qi X, Li J, Zhou C, Lv C and Tian M: MiR-142-3p suppresses SOCS6 expression and promotes cell proliferation in nasopharyngeal carcinoma. Cell Physiol Biochem. 36:1743–1752. 2015. View Article : Google Scholar : PubMed/NCBI
25	Pelloni M, Coltrinari G, Paoli D, Pallotti F, Lombardo F, Lenzi A and Gandini L: Differential expression of miRNAs in the seminal plasma and serum of testicular cancer patients. Endocrine. Oct 28–2016.(Epub ahead of print). https://doi.org/10.1007/s12020-016-1150-z View Article : Google Scholar : PubMed/NCBI
26	Summerer I, Unger K, Braselmann H, Schuettrumpf L, Maihoefer C, Baumeister P, Kirchner T, Niyazi M, Sage E, Specht HM, et al: Circulating microRNAs as prognostic therapy biomarkers in head and neck cancer patients. Br J Cancer. 113:76–82. 2015. View Article : Google Scholar : PubMed/NCBI
27	Lin RJ, Xiao DW, Liao LD, Chen T, Xie ZF, Huang WZ, Wang WS, Jiang TF, Wu BL, Li EM, et al: MiR-142-3p as a potential prognostic biomarker for esophageal squamous cell carcinoma. J Surg Oncol. 105:175–182. 2012. View Article : Google Scholar : PubMed/NCBI
28	Li Y, Chen D, Jin LU, Liu J, Li Y, Su Z, Qi Z, Shi M, Jiang Z, Yang S, et al: Oncogenic microRNA-142-3p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma. Oncol Lett. 11:1235–1241. 2016.PubMed/NCBI
29	Isobe T, Hisamori S, Hogan DJ, Zabala M, Hendrickson DG, Dalerba P, Cai S1, Scheeren F, Kuo AH1, Sikandar SS, et al: miR-142 regulates the tumorigenicity of human breast cancer stem cells through the canonical WNT signaling pathway. Elife. 3:doi: 10.7554/eLife.01977. 2014. View Article : Google Scholar : PubMed/NCBI
30	Schwickert A, Weghake E, Brüggemann K, Engbers A, Brinkmann BF, Kemper B, Seggewiß J, Stock C, Ebnet K, Kiesel L, et al: microRNA miR-142-3p inhibits breast cancer cell invasiveness by synchronous targeting of WASL, integrin alpha V, and additional cytoskeletal elements. PLoS One. 10:e01439932015. View Article : Google Scholar : PubMed/NCBI
31	Xiao P and Liu WL: MiR-142-3p functions as a potential tumor suppressor directly targeting HMGB1 in non-small-cell lung carcinoma. Int J Clin Exp Pathol. 8:10800–10807. 2015.PubMed/NCBI
32	Wu L, Cai C, Wang X, Liu M, Li X and Tang H: MicroRNA-142-3p, a new regulator of RAC1, suppresses the migration and invasion of hepatocellular carcinoma cells. FEBS Lett. 585:1322–1330. 2011. View Article : Google Scholar : PubMed/NCBI
33	Yoon CH, Hyun KH, Kim RK, Lee H, Lim EJ, Chung HY, An S, Park MJ, Suh Y, Kim MJ, et al: The small GTPase Rac1 is involved in the maintenance of stemness and malignancies in glioma stem-like cells. FEBS Lett. 585:2331–2338. 2011. View Article : Google Scholar : PubMed/NCBI
34	Zhong J, Bach CT, Shum MS and O'Neill GM: NEDD9 regulates 3D migratory activity independent of the Rac1 morphology switch in glioma and neuroblastoma. Mol Cancer Res. 12:264–273. 2014. View Article : Google Scholar : PubMed/NCBI
35	Man J, Shoemake J, Zhou W, Fang X, Wu Q, Rizzo A, Prayson R, Bao S, Rich JN and Yu JS: Sema3C promotes the survival and tumorigenicity of glioma stem cells through Rac1 activation. Cell Rep. 9:1812–1826. 2014. View Article : Google Scholar : PubMed/NCBI