Tumor suppressor miR-149-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma

Jin,Lu; Li,Yifan; Liu,Jiaju; Yang,Shangqi; Gui,Yaoting; Mao,Xiangming; Nie,Guohui; Lai,Yongqing

doi:10.3892/mmr.2016.5205

Tumor suppressor miR-149-5p is associated with cellular migration, proliferation and apoptosis in renal cell carcinoma

Authors:
- Lu Jin
- Yifan Li
- Jiaju Liu
- Shangqi Yang
- Yaoting Gui
- Xiangming Mao
- Guohui Nie
- Yongqing Lai
View Affiliations

Affiliations: The Second Clinical College, Anhui Medical University, Anhui, Hefei 230032, P.R. China, Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Department of Otolaryngology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
Published online on: April 28, 2016 https://doi.org/10.3892/mmr.2016.5205
Pages: 5386-5392

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Several studies have recently explored the role of microRNAs (miRNAs, miRs) in the tumorigenesis of various types of cancer. miRNAs have been reported to be involved in numerous cell processes, including cell apoptosis, proliferation and migration, thus suggesting that miRNAs may have an important role in cancer progression. Downregulation of miR-149-5p has been detected in RCC tissues by microarray profiling; however, its expression and function in RCC has yet to be elucidated. In the present study, reverse transcription‑quantitative polymerase chain reaction was performed to detect the expression levels of miR‑149‑5p in RCC tissues and paired normal tissues. In order to determine whether miR-149-5p was able to regulate cell proliferation, apoptosis or migration, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometric and wound healing assays were conducted. The results demonstrated that miR‑149‑5p was significantly downregulated in RCC tissues compared with in normal tissues (P<0.05). The restoration of miR-149-5p expression using synthetic mimics suppressed cell proliferation and migration, and promoted cell apoptosis. These results indicated that miR‑149‑5p may act as a tumor suppressor in RCC. The present study is the first, to the best of our knowledge, to identify miR‑149‑5p as a tumor suppressor in RCC. Future studies will be focused on the potential role of miR‑149‑5p as a biomarker for the early detection and prognostic prediction of RCC, and as a therapeutic target in RCC. In addition, further exploration regarding the pathways underlying the effects of miR‑149‑5p in RCC is required.

View Figures

View References

1	Coskun M, Bjerrum JT, Seidelin JB, Troelsen JT, Olsen J and Nielsen OH: miR-20b, miR-98, miR-125b-1, and let-7e as new potential diagnostic biomarkers in ulcerative colitis. World J Gastroenterol. 19:4289–4299. 2013. View Article : Google Scholar : PubMed/NCBI
2	Jeon YJ, Kim OJ, Kim SY, Oh SH, Oh D, Kim OJ, Shin BS and Kim NK: Association of the miR-146a, miR-149, miR-196a2, and miR-499 polymorphisms with ischemic stroke and silent brain infarction risk. Arterioscler Thromb Vasc Biol. 33:420–430. 2013. View Article : Google Scholar
3	Deng S, Zhang Y, Xu C and Ma D: MicroRNA-125b-2 over-expression represses ectodermal differentiation of mouse embryonic stem cells. Int J Mol Med. 36:355–362. 2015.PubMed/NCBI
4	Li J, Liang H, Bai M, Ning T, Wang C, Fan Q, Wang Y, Fu Z, Wang N, Liu R, et al: miR-135b promotes cancer progression by targeting transforming growth factor beta receptor II (TGFBR2) in colorectal cancer. PloS One. 10:e01301942015. View Article : Google Scholar : PubMed/NCBI
5	Xu L, Zhou X, Qiu MT, Yin R, Wu YQ and Xu L: Lack of association between hsa-miR-149 rs2292832 polymorphism and cancer risk: A meta-analysis of 12 studies. PloS One. 8:e737622013. View Article : Google Scholar : PubMed/NCBI
6	Zhang MW, Jin MJ, Yu YX, Zhang SC, Liu B, Jiang X, Pan YF, Li QI, Ma SY and Chen K: Associations of lifestyle-related factors, hsa-miR-149 and hsa-miR-605 gene polymorphisms with gastrointestinal cancer risk. Mol Carcinog. 51(Suppl 1): E21–E31. 2012. View Article : Google Scholar
7	Chen D, Li Y, Yu Z, Li Y, Su Z, Ni L, Yang S, Gui Y and Lai Y: Downregulated microRNA-510-5p acts as a tumor suppressor in renal cell carcinoma. Mol Med Rep. 12:3061–3066. 2015.PubMed/NCBI
8	Tu HF, Liu CJ, Chang CL, Wang PW, Kao SY, Yang CC, Yu EH, Lin SC and Chang KW: The association between genetic polymorphism and the processing efficiency of miR-149 affects the prognosis of patients with head and neck squamous cell carcinoma. PloS One. 7:e516062012. View Article : Google Scholar : PubMed/NCBI
9	Matsushita R, Seki N, Chiyomaru T, Inoguchi S, Ishihara T, Goto Y, Nishikawa R, Mataki H, Tatarano S, Itesako T, et al: Tumour-suppressive microRNA-144-5p directly targets CCNE1/2 as potential prognostic markers in bladder cancer. Br J Cancer. 113:282–289. 2015. View Article : Google Scholar : PubMed/NCBI
10	Tsai MM, Wang CS, Tsai CY, Chen CY, Chi HC, Tseng YH, Chung PJ, Lin YH, Chung IH, Chen CY and Lin KH: MicroRNA-196a/-196b promote cell metastasis via negative regulation of radixin in human gastric cancer. Cancer Lett. 351:222–231. 2014. View Article : Google Scholar : PubMed/NCBI
11	Tian X, Wei Z, Wang J, Liu P, Qin Y and Zhong M: MicroRNA-429 inhibits the migration and invasion of colon cancer cells by targeting PAK6/cofilin signaling. Oncol Rep. 34:707–714. 2015.PubMed/NCBI
12	Luo Z, Zhang L, Li Z, Jiang C, Dai Y, Liu X, Zheng Y, Yu H, Xiang J and Li G: miR-149 promotes epithelial-mesenchymal transition and invasion in nasopharyngeal carcinoma cells. Zhong Nan Da Xue Xue Bao Yi Xue Ban. 36:604–609. 2011.PubMed/NCBI
13	Øster B, Linnet L, Christensen LL, Thorsen K, Ongen H, Dermitzakis ET, Sandoval J, Moran S, Esteller M, Hansen TF, et al: Non-CpG island promoter hypomethylation and miR-149 regulate the expression of SRPX2 in colorectal cancer. Int J Cancer. 132:2303–2315. 2013. View Article : Google Scholar
14	Vinci S, Gelmini S, Pratesi N, Conti S, Malentacchi F, Simi L, Pazzagli M and Orlando C: Genetic variants in miR-146a, miR-149, miR-196a2, miR-499 and their influence on relative expression in lung cancers. Clin Chem Lab Med. 49:2073–2080. 2011. View Article : Google Scholar : PubMed/NCBI
15	Santini P, Politi L, Vedova PD, Scandurra R and Scotto d'Abusco A: The inflammatory circuitry of miR-149 as a pathological mechanism in osteoarthritis. Rheumatol Int. 34:711–716. 2014. View Article : Google Scholar
16	Ali Sheikh MS, Xia K, Li F, Deng X, Salma U, Deng H, Wei Wei L, Yang TL and Peng J: Circulating miR-765 and miR-149: Potential noninvasive diagnostic biomarkers for geriatric coronary artery disease patients. Biomed Res Int. 2015:7403012015. View Article : Google Scholar : PubMed/NCBI
17	Yim NH, Jung YP, Kim A, Kim T and Ma JY: Induction of apoptotic cell death by betulin in multidrug-resistant human renal carcinoma cells. Oncol Rep. 34:1058–1064. 2015.PubMed/NCBI
18	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
19	Hong MH, Kim HS, Kim C, Ahn JR, Chon HJ, Shin SJ, Ahn JB, Chung HC and Rha SY: Treatment outcomes of sunitinib treatment in advanced renal cell carcinoma patients: A single cancer center experience in Korea. Cancer Res Treat. 41:67–72. 2009. View Article : Google Scholar : PubMed/NCBI
20	Xiao W, Gao Z, Duan Y, Yuan W and Ke Y: Downregulation of miR-19a exhibits inhibitory effects on metastatic renal cell carcinoma by targeting PIK3CA and inactivating Notch signaling in vitro. Oncol Rep. 34:739–746. 2015.PubMed/NCBI
21	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
22	Lu YC, Chang JT, Huang YC, Huang CC, Chen WH, Lee LY, Huang BS, Chen YJ, Li HF and Cheng AJ: Combined determination of circulating miR-196a and miR-196b levels produces high sensitivity and specificity for early detection of oral cancer. Clin Biochem. 48:115–121. 2015. View Article : Google Scholar
23	Chow TF, Mankaruos M, Scorilas A, Youssef Y, Girgis A, Mossad S, Metias S, Rofael Y, Honey RJ, Stewart R, et al: The miR-17-92 cluster is over expressed in and has an oncogenic effect on renal cell carcinoma. J Urol. 183:743–751. 2010. View Article : Google Scholar
24	Maher ER: Genomics and epigenomics of renal cell carcinoma. Semin Cancer Biol. 23:10–17. 2013. View Article : Google Scholar
25	Ke Y, Zhao W, Xiong J and Cao R: miR-149 inhibits non-small-cell lung cancer cells EMT by targeting FOXM1. Biochem Res Int. 2013:5067312013. View Article : Google Scholar : PubMed/NCBI
26	Wang F, Ma YL, Zhang P, Shen TY, Shi CZ, Yang YZ, Moyer MP, Zhang HZ, Chen HQ, Liang Y and Qin HL: SP1 mediates the link between methylation of the tumour suppressor miR-149 and outcome in colorectal cancer. J Pathol. 229:12–24. 2013. View Article : Google Scholar
27	She X, Yu Z, Cui Y, Lei Q, Wang Z, Xu G, Xiang J, Wu M and Li G: miR-128 and miR-149 enhance the chemosensitivity of temozolomide by Rap1B-mediated cytoskeletal remodeling in glioblastoma. Oncol Rep. 32:957–964. 2014.PubMed/NCBI
28	Liu H, Brannon AR, Reddy AR, Alexe G, Seiler MW, Arreola A, Oza JH, Yao M, Juan D, Liou LS, et al: Identifying mRNA targets of microRNA dysregulated in cancer: With application to clear cell renal cell carcinoma. BMC Syst Biol. 4:512010. View Article : Google Scholar : PubMed/NCBI
29	He DX, Gu XT, Li YR, Jiang L, Jin J and Ma X: Methylation-regulated miR-149 modulates chemoresistance by targeting GlcNAc N-deacetylase/N-sulfotransferase-1 in human breast cancer. FEBS J. 281:4718–4730. 2014. View Article : Google Scholar : PubMed/NCBI
30	Wang Y, Zheng X, Zhang Z, Zhou J, Zhao G, Yang J, Xia L, Wang R, Cai X, Hu H, et al: MicroRNA-149 inhibits proliferation and cell cycle progression through the targeting of ZBTB2 in human gastric cancer. PloS One. 7:e416932012. View Article : Google Scholar : PubMed/NCBI
31	Hu Z, Chen J, Tian T, Zhou X, Gu H, Xu L, Zeng Y, Miao R, Jin G, Ma H, et al: Genetic variants of miRNA sequences and non-small cell lung cancer survival. J Clin Invest. 118:2600–2608. 2008.PubMed/NCBI
32	Huang GL, Lu Y, Pu XX, He YX, Chen ML, Li YZ, Tang SY, Che H and He Z: Association study between miR-149 gene polymorphism and nasopharyngeal carcinoma. Biomed Rep. 1:599–603. 2013.
33	Wei WJ, Lu ZW, Li DS, Wang Y, Zhu YX, Wang ZY, Wu Y, Wang YL and Ji QH: Association of the miR-149 Rs2292832 polymorphism with papillary thyroid cancer risk and clinicopathologic characteristics in a Chinese population. Int J Mol Sci. 15:20968–20981. 2014. View Article : Google Scholar : PubMed/NCBI
34	Xu L and Tang W: The associations of nucleotide polymorphisms in mir-196a2, mir-146a, mir-149 with lung cancer risk. Cancer Biomark. 15:57–63. 2015.
35	Zhang M, Jin M, Yu Y, Zhang S, Wu Y, Liu H, Liu H, Chen B, Li Q, Ma X and Chen K: Associations of miRNA polymorphisms and female physiological characteristics with breast cancer risk in Chinese population. Eur J Cancer Care (Engl). 21:274–280. 2012. View Article : Google Scholar
36	Ding SL, Wang JX, Jiao JQ, Tu X, Wang Q, Liu F, Li Q, Gao J, Zhou QY, Gu DF and Li PF: A pre-microRNA-149 (miR-149) genetic variation affects miR-149 maturation and its ability to regulate the Puma protein in apoptosis. J Biol Chem. 288:26865–26877. 2013. View Article : Google Scholar : PubMed/NCBI