MicroRNA-140-5p promotes cell proliferation via protein kinase C isoform ε in renal cell carcinoma

doi:10.16098/j.issn.0529-1356.2019.02.008

Abstract

Abstract:

Objective To explore the role of micro RNA-140-5p(miR-140-5p) in renal cell carcinoma (RCC) tumorigenesis. Methods The expression of miR-140-5p was determined by Real-time PCR in RCC (Caki-1, ACHN, OS-RC-2 and 786-O), and compared with kidney cortex proximal tubule cell (HK-2). After Caki-1 and 786-O cells were transfected with miR-140-5p inhibitor or mimic, the cell proliferation, cell cycle and related proteins were evaluated by MTS assay, flow cytometry and Western blotting. Results Caki-1 and 786-O showed the highest and lowest expression of miR-140-5p respectively. After the level of miR-140-5p in Caki-1 cells was decreased, cell proliferation was inhibited and cell number in G₀/G₁ phase was increased significantly, along with the reduction of cyclin D, E and CDK2, 4. Furthermore, the increasing level of miR-140-5p in 786-O cells promoted cell proliferation in vitro and tumorigenesis in vivo.Moreover, microarray demonstrated that protein kinase C isoform ε(PKCε), a markedly enhanced gene in RCC cells with the changed level of miR-140-5p. The combination treatment with down-regulation of PKCε, inhibitor/mimic induced changes of cell proliferation and cell cycle arrests were marked reversed in Caki-1 and 786-O cells.Conclusion These result indicate that miR-140-5p may promote cell proliferation via PKCεin RCC.

Key words: Micro RNA-140-5p, Renal cell carcinoma, Cell proliferation, Cell cycle, Real-time PCR, Human

LIU Wei-hong YU Xiao REN Yu LIU Kai-tai LIN Chen WANG Ping. MicroRNA-140-5p promotes cell proliferation via protein kinase C isoform ε in renal cell carcinoma [J]. Acta Anatomica Sinica, 2019, 50(2): 185-191.

References

［1］ Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016\[J\]. Ca A Cancer J Clini, 2016, 66(1): 7-30.

［2］ Gong BS, Feng Q. Netrin-1:the new tumor markers in renal clear cell carcinoma ［J］. Asian Pac J Trop Med, 2015, 8(6): 488-492.

［3］ Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function ［J］. Cell, 2004, 116(2): 281-297.

［4］ Cekaite L, Eide P W, Lind GE, et al. MicroRNAs as growth regulators, their function and biomarker status in colorectal cancer ［J］. Oncotarget, 2016, 7(6): 6476-6505.

［5］ Ryou-UT, Hiroaki M, Takahiro O. The role of microRNAs in the regulation of cancer stem cells ［J］. Front Genet, 2013, 4(4): 295.

［6］ Linehan WM. The genetic basis of kidney cancer: implications for management and use of targeted therapeutic approaches ［J］. Eur Urol, 2012, 61(5): 896-898.

［7］ Petillo D, Kort EJ, Anema J, et al. MicroRNA profiling of human kidney cancer subtypes ［J］. Int J Oncol, 2009, 35(1): 109-114.

［8］ Heinzelmann J, Henning B, Sanjmyatav J, et al. Specific miRNA signatures are associated with metastasis and poor prognosis in clear cell renal cell carcinoma ［J］. World J Urol, 2011, 29(3): 367-373.

［9］ Youssef YM, White NM, Grigull J, et al. Accurate molecular classification of kidney cancer subtypes using microRNA signature ［J］. European Urology, 2011, 59(5): 721-730.

［10］ Li H, Guan SB, Lu Y, et al. MiR-140-5p inhibits synovial fibroblasts proliferation and inflammatory cytokines secretion through targeting TLR4 ［J］. Biomed Pharmacother, 2017, 96: 208-214.

［11］ Guo H, Yang S, Li S, et al. LncRNA SNHG20 promotes cell proliferation and invasion via miR-140-5pADAM10 axis in cervical cancer ［J］. Biomed Pharmacother, 2018, 102: 749-757.

［12］ Miao X, Wang Z, Chen B, et al. miR-140-5p suppresses retinoblastoma cell proliferation, migration, and invasion by targeting CEMIP and CADM3 ［J］. Cell Mol Biol, 2018, 64(6): 42-47.

［13］ Hu Y, Li Y, Wu C, et al. MicroRNA-140-5p inhibits cell proliferation and invasion by regulating VEGFA/MMP2 signaling in glioma ［J］. Tumour Biol, 2017, 39(4): 1-12.

［14］ Zhuang H, Meng X, Li Y, et al. Cyclic AMP responsive element-binding protein promotes renal cell carcinoma proliferation probablyviathe expression of spindle and kinetochore-associated protein 2 ［J］. Oncotarget, 2016, 7(13): 16325-16337.

［15］ Wang X, Ren Y, Zhuang H, et al. Decrease of phosphorylated proto-oncogene CREB at Ser 133 site inhibits growth and metastatic activity of renal cell cancer ［J］. Expert Opinion on Therapeutic Targets, 2015, 19(7): 985-995.

［16］ Chen X, Wang X, Ruan A, et al. miR-141 is a key regulator of renal cell carcinoma proliferation and metastasis by controlling EphA2 expression ［J］. Clini Cancer Res, 2014, 20(10): 2617-2630.

［17］ Croce CM, Calin GA. miRNAs, cancer, and stem cell division ［J］. Cell, 2005, 122(1): 6-7.

［18］ Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation ［J］. Cell, 2011, 144(5): 646-674.

［19］ Kahl CR, Means AR. Regulation of cell cycle progression by calcium/calmodulin-dependent pathways ［J］. Endocr Revi, 2003, 24(6): 719-736.

［20］ Wang P, Huang S, Wang F, et al. Cyclic AMP-response element regulated cell cycle arrests in cancer cells ［J］. PLoS One, 2013, 8(6): e65661.

［21］ Desdouets C, Matesic G, Molina CA, et al. Cell cycle regulation of cyclin A gene expression by the cyclic AMP-responsive transcription factors CREB and CREM ［J］. Mol Cell Biol, 1995, 71(2): 233-234.

［22］ Jaken S. Protein kinase C isozymes and substrates ［J］. Curr Opini Cell Biol, 1996, 8(2): 168-173.

［23］ Gorin MA, Pan Q. Protein kinase C epsilon: an oncogene and emerging tumor biomarker ［J］. Mol Cancer, 2009, 8:9.

［24］ Jiang Z, Kong C, Zhang Z, et al. Reduction of protein kinase C α (PKC-α) promote apoptosis via down-regulation of Dicer in bladder cancer ［J］. J Cell Mol Medi, 2015, 19(5): 1085-1093.

［25］ Wu D, Foreman TL, Gregory CW, et al. Protein kinase cepsilon has the potential to advance the recurrence of human prostate cance ［J］ r. Cancer Res, 2002, 62(8): 2423-2429.

［26］ Xu XW, Yang YL, Sun ZhL, et al. Ｒaptor promoting invasion and metastasis of breast cancer through the signaling pathway Wnt3a /β-catenin ［J］. Acta Anatomica Sinica, 2017, 48(6): 682-687.

［27］ Pan Q, Li WB, Teknos TN, et al. Targeted disruption of protein kinase Cε reduces Cell invasion and motility through inactivation of RhoA and RhoC GTPases in head and neck squamous cell carcinoma ［J］. Cancer Res, 2006, 66(19): 9379-9384.

［28］ Huang B, Cao K, Li X, et al. The expression and role of protein kinase C (PKC) epsilon in clear cell renal cell carcinoma ［J］. J Exp Clini Cancer Res, 2011, 30: 88.

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