Abstract
MicroRNA-7 (miR-7) has been described as a tumor suppressor in several human cancers, but the results of a study to identify miRNAs associated with metastatic capability in breast cancer suggested that miR-7 may be characterized as an oncogene. The present study was to determine the expression and function of miR-7 in renal cell carcinoma. Quantitative real-time polymerase chain reaction was used to validate the expressions of miR-7 in 48 paired renal cell carcinomas (RCC) and normal tissues, based on the preliminary sequencing results of miRNAs. Furthermore, the impacts of miR-7 on cell migration, proliferation and apoptosis were analyzed using wound scratch assay, MTT and flow cytometry, respectively. The results demonstrated that miR-7 was up-regulated in RCC compared with normal tissues (p = 0.001). Down-regulation of miR-7 with synthesized inhibitor inhibited cell migration in vitro, suppressed cell proliferation and induced renal cancer cell apoptosis, prompting that miR-7 could be characterized as an oncogene in RCC. The present study was the first to reveal that miR-7 was up-regulated in RCC and it played an important role in RCC by affecting cellular migration, proliferation and apoptosis. Further researches should be conducted to explore the roles and target genes of miR-7 in RCC and other cancers.
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References
Akao Y, Noguchi S, Iio A, Kojima K, Takagi T, Naoe T (2011) Dysregulation of microRNA-34a expression causes drug-resistance to 5-FU in human colon cancer DLD-1 cells. Cancer Lett 300(2):197–204. doi:10.1016/j.canlet.2010.10.006
Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z (2005) Identification of hundreds of conserved and nonconserved human microRNAs. Nat Genet 37(7):766–770. doi:10.1038/ng1590
Caporali A, Meloni M, Vollenkle C, Bonci D, Sala-Newby GB, Addis R, Spinetti G, Losa S, Masson R, Baker AH, Agami R, le Sage C, Condorelli G, Madeddu P, Martelli F, Emanueli C (2011) Deregulation of microRNA-503 contributes to diabetes mellitus-induced impairment of endothelial function and reparative angiogenesis after limb ischemia. Circulation 123(3):282–291. doi:10.1161/CIRCULATIONAHA.110.952325
Chekulaeva M, Filipowicz W (2009) Mechanisms of miRNA-mediated post-transcriptional regulation in animal cells. Curr Opin Cell Biol 21(3):452–460. doi:10.1016/j.ceb.2009.04.009
Cohen HT, McGovern FJ (2005) Renal-cell carcinoma. N Engl J Med 353(23):2477–2490. doi:10.1056/NEJMra043172
Feng S, Cong S, Zhang X, Bao X, Wang W, Li H, Wang Z, Wang G, Xu J, Du B, Qu D, Xiong W, Yin M, Ren X, Wang F, He J, Zhang B (2011) MicroRNA-192 targeting retinoblastoma 1 inhibits cell proliferation and induces cell apoptosis in lung cancer cells. Nucleic Acids Res 39(15):6669–6678. doi:10.1093/nar/gkr232
Foekens JA, Sieuwerts AM, Smid M, Look MP, de Weerd V, Boersma AW, Klijn JG, Wiemer EA, Martens JW (2008) Four miRNAs associated with aggressiveness of lymph node-negative, estrogen receptor-positive human breast cancer. Proc Natl Acad Sci USA 105(35):13021–13026. doi:10.1073/pnas.0803304105
Garzon R, Calin GA, Croce CM (2009) MicroRNAs in Cancer. Annu Rev Med 60:167–179. doi:10.1146/annurev.med.59.053006.104707
Guo LJ, Zhang QY (2012) Decreased serum miR-181a is a potential new tool for breast cancer screening. Int J Mol Med 30(3):680–686. doi:10.3892/ijmm.2012.1021
Ha TY (2011) MicroRNAs in human diseases: from cancer to cardiovascular disease. Immune netw 11(3):135–154. doi:10.4110/in.2011.11.3.135
Jemal A, Siegel R, Xu J, Ward E (2010) Cancer statistics, 2010. CA: cancer J clin 60(5):277–300. doi:10.3322/caac.20073
Jiang L, Liu X, Chen Z, Jin Y, Heidbreder CE, Kolokythas A, Wang A, Dai Y, Zhou X (2010) MicroRNA-7 targets IGF1R (insulin-like growth factor 1 receptor) in tongue squamous cell carcinoma cells. Biochem J 432(1):199–205. doi:10.1042/BJ20100859
Kefas B, Godlewski J, Comeau L, Li Y, Abounader R, Hawkinson M, Lee J, Fine H, Chiocca EA, Lawler S, Purow B (2008) microRNA-7 inhibits the epidermal growth factor receptor and the Akt pathway and is down-regulated in glioblastoma. Cancer Res 68(10):3566–3572. doi:10.1158/0008-5472.CAN-07-6639
Kim VN (2005) MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol 6(5):376–385. doi:10.1038/nrm1644
Kong X, Li G, Yuan Y, He Y, Wu X, Zhang W, Wu Z, Chen T, Wu W, Lobie PE, Zhu T (2012) MicroRNA-7 inhibits epithelial-to-mesenchymal transition and metastasis of breast cancer cells via targeting FAK expression. PLoS ONE 7(8):e41523. doi:10.1371/journal.pone.0041523
Lam JS, Leppert JT, Figlin RA, Belldegrun AS (2005) Role of molecular markers in the diagnosis and therapy of renal cell carcinoma. Urology 66(5 Suppl):1–9. doi:10.1016/j.urology.2005.06.112
Leonardi GC, Candido S, Carbone M, Colaianni V, Garozzo SF, Cina D, Libra M (2012) microRNAs and thyroid cancer: biological and clinical significance (Review). Int J Mol Med 30(5):991–999. doi:10.3892/ijmm.2012.1089
Li X, Chen J, Hu X, Huang Y, Li Z, Zhou L, Tian Z, Ma H, Wu Z, Chen M, Han Z, Peng Z, Zhao X, Liang C, Wang Y, Sun L, Zhao J, Jiang B, Yang H, Gui Y, Cai Z, Zhang X (2011) Comparative mRNA and microRNA expression profiling of three genitourinary cancers reveals common hallmarks and cancer-specific molecular events. PLoS ONE 6(7):e22570. doi:10.1371/journal.pone.0022570
Liu X, Yu J, Jiang L, Wang A, Shi F, Ye H, Zhou X (2009) MicroRNA-222 regulates cell invasion by targeting matrix metalloproteinase 1 (MMP1) and manganese superoxide dismutase 2 (SOD2) in tongue squamous cell carcinoma cell lines. Cancer Genomics Proteomics 6(3):131–139
Liu M, Tang Q, Qiu M, Lang N, Li M, Zheng Y, Bi F (2011) miR-21 targets the tumor suppressor RhoB and regulates proliferation, invasion and apoptosis in colorectal cancer cells. FEBS Lett 585(19):2998–3005. doi:10.1016/j.febslet.2011.08.014
Maes OC, Chertkow HM, Wang E, Schipper HM (2009) MicroRNA: implications for Alzheimer disease and other human CNS disorders. Curr Genomics 10(3):154–168. doi:10.2174/138920209788185252
Makeyev EV, Maniatis T (2008) Multilevel regulation of gene expression by microRNAs. Science 319(5871):1789–1790. doi:10.1126/science.1152326
Motzer RJ, Bander NH, Nanus DM (1996) Renal-cell carcinoma. N Engl J med 335(12):865–875. doi:10.1056/NEJM199609193351207
Patel C, Ahmed A, Ellsworth P (2012) Renal cell carcinoma: a reappraisal. Urol nurs 32(4):182–190 quiz 191
Reddy SD, Ohshiro K, Rayala SK, Kumar R (2008) MicroRNA-7, a homeobox D10 target, inhibits p21-activated kinase 1 and regulates its functions. Cancer Res 68(20):8195–8200. doi:10.1158/0008-5472.CAN-08-2103
Rouviere O, Bouvier R, Negrier S, Badet L, Lyonnet D (2006) Nonmetastatic renal-cell carcinoma: is it really possible to define rational guidelines for post-treatment follow-up? Nat Clin Pract Oncol 3(4):200–213. doi:10.1038/ncponc0479
Shibuya H, Iinuma H, Shimada R, Horiuchi A, Watanabe T (2010) Clinicopathological and prognostic value of microRNA-21 and microRNA-155 in colorectal cancer. Oncology 79(3–4):313–320. doi:10.1159/000323283
Soeda S, Ohyashiki JH, Ohtsuki K, Umezu T, Setoguchi Y, Ohyashiki K (2013) Clinical relevance of plasma miR-106b levels in patients with chronic obstructive pulmonary disease. Int J Mol Med 31(3):533–539. doi:10.3892/ijmm.2013.1251
Tili E, Michaille JJ, Wernicke D, Alder H, Costinean S, Volinia S, Croce CM (2011) Mutator activity induced by microRNA-155 (miR-155) links inflammation and cancer. Proc Natl Acad Sci USA 108(12):4908–4913. doi:10.1073/pnas.1101795108
Ventura A, Jacks T (2009) MicroRNAs and cancer: short RNAs go a long way. Cell 136(4):586–591. doi:10.1016/j.cell.2009.02.005
Wang GK, Zhu JQ, Zhang JT, Li Q, Li Y, He J, Qin YW, Jing Q (2010) Circulating microRNA: a novel potential biomarker for early diagnosis of acute myocardial infarction in humans. Eur Heart J 31(6):659–666. doi:10.1093/eurheartj/ehq013
Webster RJ, Giles KM, Price KJ, Zhang PM, Mattick JS, Leedman PJ (2009) Regulation of epidermal growth factor receptor signaling in human cancer cells by microRNA-7. J biol chem 284(9):5731–5741. doi:10.1074/jbc.M804280200
Wulfken LM, Moritz R, Ohlmann C, Holdenrieder S, Jung V, Becker F, Herrmann E, Walgenbach-Brunagel G, von Ruecker A, Muller SC, Ellinger J (2011) MicroRNAs in renal cell carcinoma: diagnostic implications of serum miR-1233 levels. PLoS ONE 6(9):e25787. doi:10.1371/journal.pone.0025787
Xiong Y, Zhang L, Holloway AK, Wu X, Su L, Kebebew E (2011) MiR-886-3p regulates cell proliferation and migration, and is dysregulated in familial non-medullary thyroid cancer. PLoS ONE 6(10):e24717. doi:10.1371/journal.pone.0024717
Zhai Q, Zhou L, Zhao C, Wan J, Yu Z, Guo X, Qin J, Chen J, Lu R (2012) Identification of miR-508-3p and miR-509-3p that are associated with cell invasion and migration and involved in the apoptosis of renal cell carcinoma. Biochem Biophys Res Commun 419(4):621–626. doi:10.1016/j.bbrc.2012.02.060
Zhao P, Dai M, Chen W, Li N (2010) Cancer trends in China. Jpn J Clin Oncol 40(4):281–285. doi:10.1093/jjco/hyp187
Zhou L, Chen J, Li Z, Li X, Hu X, Huang Y, Zhao X, Liang C, Wang Y, Sun L, Shi M, Xu X, Shen F, Chen M, Han Z, Peng Z, Zhai Q, Zhang Z, Yang R, Ye J, Guan Z, Yang H, Gui Y, Wang J, Cai Z, Zhang X (2010) Integrated profiling of microRNAs and mRNAs: microRNAs located on Xq27.3 associate with clear cell renal cell carcinoma. PLoS ONE 5(12):e15224. doi:10.1371/journal.pone.0015224
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No.81101922), Medical Scientific Research Foundation of Guangdong Province of China (No. A2012584) and Natural Science Foundation of Guangdong Province of China (No.S2012010008365).
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Zuhu Yu and Liangchao Ni contributed equally to this work.
Yongqing Lai is the primary corresponding author.
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Yu, Z., Ni, L., Chen, D. et al. Identification of miR-7 as an oncogene in renal cell carcinoma. J Mol Hist 44, 669–677 (2013). https://doi.org/10.1007/s10735-013-9516-5
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DOI: https://doi.org/10.1007/s10735-013-9516-5