miR-125b is associated with renal cell carcinoma cell migration, invasion and apoptosis

Jin,Lu; Zhang,Zeng; Li,Yifan; He,Tao; Hu,Jia; Liu,Jiaju; Chen,Mingwei; Gui,Yaoting; Chen,Yun; Lai,Yongqing

doi:10.3892/ol.2017.5985

miR-125b is associated with renal cell carcinoma cell migration, invasion and apoptosis

Authors:
- Lu Jin
- Zeng Zhang
- Yifan Li
- Tao He
- Jia Hu
- Jiaju Liu
- Mingwei Chen
- Yaoting Gui
- Yun Chen
- Yongqing Lai
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Affiliations: Department of Urology, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China, Department of Urology, Anhui Medical University, Hefei, Anhui 230032, P.R. China, The Guangdong and Shenzhen Key Laboratory of Male Reproductive Medicine and Genetics, Shenzhen, Guangdong 518036, P.R. China, Department of Ultrasound, Peking University Shenzhen Hospital, Shenzhen, Guangdong 518036, P.R. China
Published online on: April 4, 2017 https://doi.org/10.3892/ol.2017.5985
Pages: 4512-4520

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Abstract

MicroRNA (miR)-125b has been identified as deregulated in a number of types of cancer. Previous studies have detected the expression of miR-125b in clear cell renal cell carcinoma (ccRCC) tissues by in situ hybridization and revealed that miR-125b was upregulated in ccRCC tissues, and was associated with recurrence and survival of patients with ccRCC. However, the function of miR‑125b in RCC remains unclear. Thus, the expression of miR‑125b was detected with quantitative polymerase chain reaction (qPCR) in 24 paired RCC and adjacent normal tissues. The result of qPCR showed that miR‑125b was upregulated in RCC tissues. Furthermore, the function of miR‑125b in RCC (786‑O and ACHN) cells was detected by transfecting miR‑125 mimic or inhibitor to upregulate or downregulate miR‑125b expression. Cell proliferation assays (MTT and Cell Counting Kit‑8), cell mobility assays (cell scratch and Transwell assay) and a cell apoptotic assay (flow cytometry assay) were performed to assess the function of miR‑125b on RCC cells. Results from the assays demonstrated that overexpression of miR‑125b could promote cell migration and invasion, and reduce the cell apoptotic rate. It was also revealed that downregulation of miR‑125b could reduce cell migration and invasion, and induce cell apoptosis. However, the results of the cell proliferation assay revealed that miR‑125b had no significant effect on cell proliferation. Not only could miR‑125b predict recurrence and survival of ccRCC; the present study revealed that miR‑125b could regulate RCC cell migration, invasion and apoptosis. Additional studies are required to determine the mechanism of miR‑125b in RCC cells and define the target genes of miR‑125b in RCC.

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1	Tostain J, Li G, Gentil-Perret A and Gigante M: Carbonic anhydrase 9 in clear cell renal cell carcinoma: A marker for diagnosis, prognosis and treatment. Eur J Cancer. 46:3141–3148. 2010. View Article : Google Scholar : PubMed/NCBI
2	Hadoux J, Vignot S and De La Motte Rouge T: Renal cell carcinoma: Focus on safety and efficacy of temsirolimus. Clin Med Insights Oncol. 4:143–154. 2010. View Article : Google Scholar : PubMed/NCBI
3	Su Z, Chen D, Zhang E, Li Y, Yu Z, Shi M, Jiang Z, Ni L, Yang S, Gui Y, et al: MicroRNA-509-3p inhibits cancer cell proliferation and migration by targeting the mitogen-activated protein kinase kinase kinase 8 oncogene in renal cell carcinoma. Mol Med Rep. 12:1535–1543. 2015.PubMed/NCBI
4	Alt AL, Boorjian SA, Lohse CM, Costello BA, Leibovich BC and Blute ML: Survival after complete surgical resection of multiple metastases from renal cell carcinoma. Cancer. 117:2873–2882. 2011. View Article : Google Scholar : PubMed/NCBI
5	Rasmussen F: Metastatic renal cell cancer. Cancer Imaging. 13:374–380. 2013. View Article : Google Scholar : PubMed/NCBI
6	Zou X, Zhong J, Li J, Su Z, Chen Y, Deng W, Li Y, Lu S, Lin Y, Luo L, et al: miR-362-3p targets nemo-like kinase and functions as a tumor suppressor in renal cancer cells. Mol Med Rep. 13:994–1002. 2016.PubMed/NCBI
7	Jiang JX, Gao S, Pan YZ, Yu C and Sun CY: Overexpression of microRNA-125b sensitizes human hepatocellular carcinoma cells to 5-fluorouracil through inhibition of glycolysis by targeting hexokinase II. Mol Med Rep. 10:995–1002. 2014.PubMed/NCBI
8	Akman HB, Selcuklu SD, Donoghue MT, Akhavantabasi S, Sapmaz A, Spillane C, Yakicier MC and Erson-Bensan AE: ALCAM is indirectly modulated by miR-125b in MCF7 cells. Tumour Biol. 36:3511–3520. 2015. View Article : Google Scholar : PubMed/NCBI
9	Yang Q, Wang Y, Lu X, Zhao Z, Zhu L, Chen S, Wu Q, Chen C and Wang Z: MiR-125b regulates epithelial-mesenchymal transition via targeting Sema4C in paclitaxel-resistant breast cancer cells. Oncotarget. 6:3268–3279. 2015. View Article : Google Scholar : PubMed/NCBI
10	Wei X, Chen D, Lv T, Li G and Qu S: Serum microRNA-125b as a potential biomarker for glioma diagnosis. Mol Neurobiol. 53:163–170. 2016. View Article : Google Scholar : PubMed/NCBI
11	Iwamoto H, Kanda Y, Sejima T, Osaki M, Okada F and Takenaka A: Serum miR-210 as a potential biomarker of early clear cell renal cell carcinoma. Int J Oncol. 44:53–58. 2014.PubMed/NCBI
12	Karbasy SH, Taheriazam A, Mirghasemi A, Sedaghati F, Shakeri M, Yahaghi E and Bahador R: RETRACTED ARTICLE: Upregulation of miR-300 and downregulation of miR-125b act as potential predictor biomarkers in progression, metastasis, and poor prognosis of osteosarcoma. Tumour Biol. Sep 2–2015.(Epub ahead of print). PubMed/NCBI
13	Tsang FH, Au V, Lu WJ, Shek FH, Liu AM, Luk JM, Fan ST, Poon RT and Lee NP: Prognostic marker microRNA-125b inhibits tumorigenic properties of hepatocellular carcinoma cells via suppressing tumorigenic molecule eIF5A2. Dig Dis Sci. 59:2477–2487. 2014. View Article : Google Scholar : PubMed/NCBI
14	He H, Xu F, Huang W, Luo SY, Lin YT, Zhang GH, Du Q and Duan RH: miR-125a-5p expression is associated with the age of breast cancer patients. Genet Mol Res. 14:17927–17933. 2015. View Article : Google Scholar : PubMed/NCBI
15	Wang F, Yu D, Liu Z, Wang R, Xu Y, Cui H and Zhao T: miR-125b functions as a tumor suppressor and enhances chemosensitivity to cisplatin in osteosarcoma. Technol Cancer Res Treat. 15:NP105–NP112. 2016. View Article : Google Scholar : PubMed/NCBI
16	Wu JG, Wang JJ, Jiang X, Lan JP, He XJ, Wang HJ, Ma YY, Xia YJ, Ru GQ, Ma J, et al: MiR-125b promotes cell migration and invasion by targeting PPP1CA-Rb signal pathways in gastric cancer, resulting in a poor prognosis. Gastric Cancer. 18:729–739. 2015. View Article : Google Scholar : PubMed/NCBI
17	Fu Q, Liu Z, Pan D, Zhang W, Xu L, Zhu Y, Liu H and Xu J: Tumor miR-125b predicts recurrence and survival of patients with clear-cell renal cell carcinoma after surgical resection. Cancer Sci. 105:1427–1434. 2014. View Article : Google Scholar : PubMed/NCBI
18	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
19	Li Q, Han Y, Wang C, Shan S, Wang Y, Zhang J and Ren T: MicroRNA-125b promotes tumor metastasis through targeting tumor protein 53-induced nuclear protein 1 in patients with non-small-cell lung cancer. Cancer Cell Int. 15:842015. View Article : Google Scholar : PubMed/NCBI
20	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 Sys Biol. 4:512010. View Article : Google Scholar
21	He H, Wang L, Zhou W, Zhang Z, Wang L, Xu S, Wang D, Dong J, Tang C, Tang H, et al: MicroRNA expression profiling in clear cell renal cell carcinoma: Identification and functional validation of key miRNAs. PLoS One. 10:e01256722015. View Article : Google Scholar : PubMed/NCBI
22	Juan D, Alexe G, Antes T, Liu H, Madabhushi A, Delisi C, Ganesan S, Bhanot G and Liou LS: Identification of a microRNA panel for clear-cell kidney cancer. Urology. 75:835–841. 2010. View Article : Google Scholar : PubMed/NCBI
23	Heinzelmann J, Henning B, Sanjmyatav J, Posorski N, Steiner T, Wunderlich H, Gajda MR and Junker K: Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma. World J Urol. 29:367–373. 2011. View Article : Google Scholar : PubMed/NCBI
24	Lee M, Kim EJ and Jeon MJ: MicroRNAs 125a and 125b inhibit ovarian cancer cells through post-transcriptional inactivation of EIF4EBP1. Oncotarget. 7:8726–8742. 2016.PubMed/NCBI
25	Tsang FH, Au SL, Wei L, Fan DN, Lee JM, Wong CC, Ng IO and Wong CM: Long non-coding RNA HOTTIP is frequently up-regulated in hepatocellular carcinoma and is targeted by tumour suppressive miR-125b. Liver Int. 35:1597–1606. 2015. View Article : Google Scholar : PubMed/NCBI
26	Wu S, Liu F, Xie L, Peng Y, Lv X, Zhu Y, Zhang Z and He X: miR-125b suppresses proliferation and invasion by targeting MCL1 in gastric cancer. Biomed Res Int. 2015:3652732015. View Article : Google Scholar : PubMed/NCBI
27	Zang B, Huang G, Wang X and Zheng S: HPV-16 E6 promotes cell growth of esophageal cancer via downregulation of miR-125b and activation of Wnt/β-catenin signaling pathway. Int J Clin Exp Pathol. 8:13687–13694. 2015.PubMed/NCBI
28	Wang X, Zhang Y, Fu Y, Zhang J, Yin L, Pu Y and Liang G: MicroRNA-125b may function as an oncogene in lung cancer cells. Mol Med Rep. 11:3880–3887. 2015.PubMed/NCBI
29	Wang M, Zhu X, Sha Z, Li N, Li D and Chen L: High expression of kinesin light chain-2, a novel target of miR-125b, is associated with poor clinical outcome of elderly non-small-cell lung cancer patients. Br J Cancer. 112:874–882. 2015. View Article : Google Scholar : PubMed/NCBI
30	Lehmann TP, Korski K, Gryczka R, Ibbs M, Thieleman A, Grodecka-Gazdecka S and Jagodziński PP: Relative levels of let-7a, miR-17, miR-27b, miR-125a, miR-125b and miR-206 as potential molecular markers to evaluate grade, receptor status and molecular type in breast cancer. Mol Med Rep. 12:4692–4702. 2015.PubMed/NCBI
31	Vilquin P, Donini CF, Villedieu M, Grisard E, Corbo L, Bachelot T, Vendrell JA and Cohen PA: MicroRNA-125b upregulation confers aromatase inhibitor resistance and is a novel marker of poor prognosis in breast cancer. Breast Cancer Res. 17:132015. View Article : Google Scholar : PubMed/NCBI
32	Chen H and Xu Z: Hypermethylation-associated silencing of miR-125a and miR-125b: A potential marker in colorectal cancer. Dis Markers. 2015:3450802015. View Article : Google Scholar : PubMed/NCBI
33	Yamada A, Horimatsu T, Okugawa Y, Nishida N, Honjo H, Ida H, Kou T, Kusaka T, Sasaki Y, Yagi M, et al: Serum miR-21, miR-29a, and miR-125b are promising biomarkers for the early detection of colorectal neoplasia. Clin Cancer Res. 21:4234–4242. 2015. View Article : Google Scholar : PubMed/NCBI
34	Ribeiro J, Marinho-Dias J, Monteiro P, Loureiro J, Baldaque I, Medeiros R and Sousa H: miR-34a and miR-125b expression in HPV infection and cervical cancer development. Biomed Res Int. 2015:3045842015. View Article : Google Scholar : PubMed/NCBI
35	Chen X, Liu J, Feng WK, Wu X and Chen SY: MiR-125b protects against ethanol-induced apoptosis in neural crest cells and mouse embryos by targeting Bak 1 and PUMA. Exp Neurol. 271:104–111. 2015. View Article : Google Scholar : PubMed/NCBI
36	Xie X, Hu Y, Xu L, Fu Y, Tu J, Zhao H, Zhang S, Hong R and Gu X: The role of miR-125b-mitochondria-caspase-3 pathway in doxorubicin resistance and therapy in human breast cancer. Tumour Biol. 36:7185–7194. 2015. View Article : Google Scholar : PubMed/NCBI
37	Morelli E, Leone E, Cantafio ME, Di Martino MT, Amodio N, Biamonte L, Gullàà A, Foresta U, Pitari MR, Botta C, et al: Selective targeting of IRF4 by synthetic microRNA-125b-5p mimics induces anti-multiple myeloma activity in vitro and in vivo. Leukemia. 29:2173–2183. 2015. View Article : Google Scholar : PubMed/NCBI