Identification of miR‑30b as an oncogene in renal cell carcinoma

Jin,Lu; Li,Yifan; He,Tao; Hu,Jia; Liu,Jiaju; Chen,Mingwei; Shi,Min; Jiang,Zhimao; Yang,Shangqi; Mao,Xiangming; Gui,Yaoting; Lai,Yongqing

doi:10.3892/mmr.2017.6197

Identification of miR‑30b as an oncogene in renal cell carcinoma

Authors:
- Lu Jin
- Yifan Li
- Tao He
- Jia Hu
- Jiaju Liu
- Mingwei Chen
- Min Shi
- Zhimao Jiang
- Shangqi Yang
- Xiangming Mao
- Yaoting Gui
- Yongqing Lai
View Affiliations

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, Peking University Shenzhen Hospital, Institute of Urology of Shenzhen PKU‑HKUST Medical Center, Shenzhen, Guangdong 518036, P.R. China
Published online on: February 13, 2017 https://doi.org/10.3892/mmr.2017.6197
Pages: 1837-1846

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

microRNAs (miRs) have been investigated as a novel class of regulators of cellular processes, including proliferation, apoptosis and metabolism. In particular, miR‑30b has been demonstrated to be deregulated in certain types of cancer, including lung, colorectal and gastric cancer. Previous studies of miR‑30b in renal clear cell carcinoma demonstrated that the expression level of miR‑30b was associated with distant metastasis. However, the function of miR‑30b in renal cell carcinoma (RCC) remained to be elucidated. In the present study, the expression of miR‑30b in 31 paired RCC tissues from four cell lines (786‑O, 769‑P, ACHN and 293T) was detected by reverse transcription‑quantitative polymerase chain reaction. In addition, the effect of miR‑30b on cell proliferation in RCC cells was also determined using MTT and Cell Counting Kit‑8 assay analyses. Furthermore, the function of miR‑30b in cell migration and invasion was determined by wound scratch and Transwell assays. Flow cytometry was also performed to quantify the effect of miR‑30b on cell apoptosis. The results of the current study indicated that miR‑30b was upregulated in RCC tissues from affected cell lines when compared with adjacent normal tissues and a normal kidney cell line, which is different to the downregulation of miR‑30b as observed in other types of cancer. miR‑30b is associated with RCC cell proliferation, invasion, migration and apoptosis, which indicated that miR‑30b acts as an oncogene in RCC. To the best of our knowledge, the present study is the first to demonstrate the upregulation of miR‑30b in RCC tissues and describe miR‑30b as an oncogene in RCC in the regulation of cell proliferation, migration, invasion and apoptosis. Further studies will define the target gene of miR‑30b in RCC and investigate the potential role of miR‑30b as a biomarker for RCC.

View Figures

View References

1	Laitinen M, Parry M, Ratasvuori M, Wedin R, Albergo JI, Jeys L, Abudu A, Carter S, Gaston L, Tillman R and Grimer R: Survival and complications of skeletal reconstructions after surgical treatment of bony metastatic renal cell carcinoma. EJSO the Journal Cancer Surgery. 41:886–892. 2015.
2	Siegel R, Naishadham D and Jemal A: Cancer statistics, 2013. CA Cancer J Clin. 63:11–30. 2013. View Article : Google Scholar : PubMed/NCBI
3	Rasmussen F: Metastatic renal cell cancer. Cancer Imaging. 13:374–380. 2013. View Article : Google Scholar : PubMed/NCBI
4	Rouvière O, Bouvier R, Négrier S, Badet L and Lyonnet D: Nonmetastatic renal-cell carcinoma: Is it really possible to define rational guidelines for post-treatment follow-up? Nat Clin Pract Oncol. 3:200–213. 2006. View Article : Google Scholar : PubMed/NCBI
5	Bianchi M, Sun M, Jeldres C, Shariat SF, Trinh QD, Briganti A, Tian Z, Schmitges J, Graefen M, Perrotte P, et al: Distribution of metastatic sites in renal cell carcinoma: A population-based analysis. Ann Oncol. 23:973–980. 2012. View Article : Google Scholar : PubMed/NCBI
6	Wang Q, Zhang W, Yang J, Liu YL, Yan ZX, Guo ZJ, Li YJ and Bian XW: High ERα36 Expression level and membrane location predict poor prognosis in renal cell carcinoma. Medicine (Baltimore). 94:e10482015. View Article : Google Scholar : PubMed/NCBI
7	Zhang HM, Yang FQ, Chen SJ, Che J and Zheng JH: Upregulation of long non-coding RNA MALAT1 correlates with tumor progression and poor prognosis in clear cell renal cell carcinoma. Tumour Biol. 36:2947–2955. 2015. View Article : Google Scholar : PubMed/NCBI
8	Schaefer A, Jung M, Kristiansen G, Lein M, Schrader M, Miller K, Stephan C and Jung K: MicroRNAs and cancer: Current state and future perspectives in urologic oncology. Urol Oncol. 28:4–13. 2010. View Article : Google Scholar : PubMed/NCBI
9	Mu YP, Tang S, Sun WJ, Gao WM, Wang M and Su XL: Association of miR-193b down-regulation and mir-196a up-regulation with clinicopathological features and prognosis in gastric Cancer. Asian Pac J Cancer Prev. 15:8893–9000. 2014. View Article : Google Scholar : PubMed/NCBI
10	Shao C, Yu Y, Yu L, Pei Y, Feng Q, Chu F, Fang Z and Zhou Y: Amplification and up-regulation of microRNA-30b in oral squamous cell cancers. Arch Oral Biol. 57:1012–1017. 2012. View Article : Google Scholar : PubMed/NCBI
11	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 : PubMed/NCBI
12	Qiao F, Zhang K, Gong P, Wang L, Hu J, Lu S and Fan H: Decreased miR-30b-5p expression by DNMT1 methylation regulation involved in gastric cancer metastasis. Mol Biol Rep. 41:5693–5700. 2014. View Article : Google Scholar : PubMed/NCBI
13	Chen S, Li P, Yang R, Cheng R, Zhang F, Wang Y, Chen X, Sun Q, Zang W, Du Y, et al: microRNA-30b inhibits cell invasion and migration through targeting collagen triple helix repeat containing 1 in non-small cell lung cancer. Cancer Cell Int. 15:852015. View Article : Google Scholar : PubMed/NCBI
14	Zhao H, Xu Z, Qin H, Gao Z and Gao L: miR-30b regulates migration and invasion of human colorectal cancer via SIX1. Biochem J. 460:117–125. 2014. View Article : Google Scholar : PubMed/NCBI
15	Zhu ED, Li N, Li BS, Li W, Zhang WJ, Mao XH, Guo G, Zou QM and Xiao B: miR-30b, down-regulated in gastric cancer, promotes apoptosis and suppresses tumor growth by targeting plasminogen activator inhibitor-1. PLoS One. 9:e1060492014. View Article : Google Scholar : PubMed/NCBI
16	Ge YZ, Wu R, Xin H, Zhu M, Lu TZ, Liu H, Xu Z, Yu P, Zhao YC, Li MH, et al: A tumor-specific microRNA signature predicts survival in clear cell renal cell carcinoma. J Cancer Res Clin Oncol. 141:1291–1299. 2015. View Article : Google Scholar : PubMed/NCBI
17	Wulfken LM, Moritz R, Ohlmann C, Holdenrieder S, Jung V, Becker F, Herrmann E, Walgenbach-Brünagel G, von Ruecker A, Müller SC and Ellinger J: MicroRNAs in renal cell carcinoma: Diagnostic implications of serum miR-1233 levels. PLoS One. 6:e257872011. 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	Wang ZX, Li JL, Cao JX, Liu YS, Li D, Zhang XY, Wang M, Wu M, Xu BL, Liu JL, et al: Cytokine-induced killer cells in the treatment of patients with renal cell carcinoma: A pooled meta-analysis. Immunotherapy. 6:787–795. 2014. View Article : Google Scholar : PubMed/NCBI
20	Liu M, Tang Q, Qiu M, Lang N, Li M, Zheng Y and Bi F: miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion and apoptosis in colorectal cancer cells. FEBS Lett. 585:2998–3005. 2011. View Article : Google Scholar : PubMed/NCBI
21	Zhong K, Chen K, Han L and Li B: MicroRNA-30b/c inhibits non-small cell lung cancer cell proliferation by targeting Rab18. BMC Cancer. 14:7032014. View Article : Google Scholar : PubMed/NCBI
22	Tian SB, Yu JC, Liu YQ, Kang WM, Ma ZQ, Ye X and Yan C: MiR-30b suppresses tumor migration and invasion by targeting EIF5A2 in gastric cancer. World J Gastroenterol. 21:9337–9347. 2015. View Article : Google Scholar : PubMed/NCBI
23	Mahdavinezhad A, Mousavi-Bahar SH, Poorolajal J, Yadegarazari R, Jafari M, Shabab N and Saidijam M: Evaluation of miR-141, miR-200c, miR-30b Expression and Clinicopathological Features of Bladder Cancer. Int J Mol Cell Med. 4:32–39. 2015.PubMed/NCBI
24	Lu Y, Ryan SL, Elliott DJ, Bignell GR, Futreal PA, Ellison DW, Bailey S and Clifford SC: Amplification and overexpression of Hsa-miR-30b, Hsa-miR-30d and KHDRBS3 at 8q24.22-q24.23 in medulloblastoma. PLoS One. 4:e61592009. View Article : Google Scholar : PubMed/NCBI
25	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
26	Gu YF, Zhang H, Su D, Mo ML, Song P, Zhang F and Zhang SC: miR-30b and miR-30c expression predicted response to tyrosine kinase inhibitors as first line treatment in non-small cell lung cancer. Chin Med J (Engl). 126:4435–4439. 2013.PubMed/NCBI
27	Liao WT, Ye YP, Zhang NJ, Li TT, Wang SY, Cui YM, Qi L, Wu P, Jiao HL, Xie YJ, et al: MicroRNA-30b functions as a tumour suppressor in human colorectal cancer by targeting KRAS, PIK3CD and BCL2. J Pathol. 232:415–427. 2014. View Article : Google Scholar : PubMed/NCBI
28	Bridge G, Monteiro R, Henderson S, Emuss V, Lagos D, Georgopoulou D, Patient R and Boshoff C: The microRNA-30 family targets DLL4 to modulate endothelial cell behavior during angiogenesis. Blood. 120:5063–5072. 2012. View Article : Google Scholar : PubMed/NCBI
29	Fuster O, Llop M, Dolz S, García P, Such E, Ibáñez M, Luna I, Gómez I, López M, Cervera J, et al: Adverse prognostic value of MYBL2 overexpression and association with microRNA-30 family in acute myeloid leukemia patients. Leuk Res. 37:1690–1696. 2013. View Article : Google Scholar : PubMed/NCBI
30	Li L and Wang B: Overexpression of microRNA-30b improves adenovirus-mediated p53 cancer gene therapy for laryngeal carcinoma. Int J Mol Sci. 15:19729–19740. 2014. View Article : Google Scholar : PubMed/NCBI
31	Ichikawa T, Sato F, Terasawa K, Tsuchiya S, Toi M, Tsujimoto G and Shimizu K: Trastuzumab produces therapeutic actions by upregulating miR-26a and miR-30b in breast cancer cells. PLoS One. 7:e314222012. View Article : Google Scholar : PubMed/NCBI