Objective To investigate the effects of miR-128-3p overexpression on invasion, migration and epithelial-mesenchymal transition of bladder cancer 5637 cells. Methods The target gene of miR-128-3p was screened by the gene prediction software TargetScan. And the luciferase reporter assay was verified. The expression of miR-128-3p and MAPK1 was detected by RT-PCR. Cell invasion was detected by Transwell. Cell migration ability was measured by a scratch test. The expressions of E-cadherin, N-cadherin, ERK1/2, c-Myc and c-fos were detected by Western blot, and the expression of Vimentin was detected by immunofluorescence. The xenograft model was established by subcutaneous injection in nude mice. The tumor weight was measured 30 days later. And the survival curve was drawn. The amount of Vimentin, miR-128-3p, MAPK1, ERK1/2, c-Myc and c-fos in the transplanted tumor was detected. Results miR-128-3p had been targeted to inhibit the expression of MAPK1. After overexpression of miR-128-3p, the number of invasive cells and wound healing rate was decreased. E-cadherin expression was up-regulated. N-cadherin expression was down-regulated. Vimentin positive was decreased. The expression of ERK1/2, c-Myc and c-fos was down-regulated. Through the intervention of miR-128-3p, the weight of transplanted tumors was decreased. The survival rate of nude mice was increased. The expression of miR-128-3p was up-regulated. The expression of MAPK1 was down-regulated. The expression of Vimentin was decreased. And the expression of ERK1/2, c-Myc and c-fos was decreased. Conclusion Overexpression of miR-128-3p inhibits the invasion, migration, epithelial-mesenchymal transition and ERK1/2, c-Myc and c-fos pathways of bladder cancer cell line 5637 by targeting inhibition of MAPK1 expression.
Key words
miR-128-3p, MAPK1 /
Bladder cancer cell line 5637 /
Invasion /
Migration /
Epithelial-mesenchymal transition
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
References
[1] Martinez Rodriguez RH, Buisan Rueda O, Ibarz L. Bladder cancer: present and future[J]. Med Clin(Barc), 2017, 149(10): 449-455.
[2] Chen C, Deng Y, Hu X, et al. Mir-128-3p regulates 3t3-l1 adipogenesis and lipolysis by targeting pparg and sertad2[J]. J Physiol Biochem, 2018, 74(3): 381-393.
[3] Chen GH, Xu CS, Zhang J, et al. Inhibition of mir-128-3p by tongxinluo protects human cardiomyocytes from ischemia/reperfusion injury via upregulation of p70s6k1/p-p70s6k1[J]. Front Pharmacol, 2017, 8(2): 775.
[4] Mao G, Ren P, Wang G, et al. Microrna-128-3p protects mouse against cerebral ischemia through reducing p38alpha mitogen-activated protein kinase activity [J]. J Mol Neurosci, 2017, 61(2): 152-158.
[5] Chen J, Li W, Li Y, et al. Microrna-128-3p impaired water maze learning by suppressing doublecortin expression in both wild type and abeta-42 infused mice[J]. Neurosci Lett, 2016, 626(1): 79-85.
[6] Xia Z, Meng F, Liu Y, et al. Decreased mir-128-3p alleviates the progression of rheumatoid arthritis by up-regulating the expression of tnfaip3[J]. Biosci Rep, 2018,38(4):31.
[7] Zhou J, He Z, Guo L, et al. Mir-128-3p directly targets vegfc/vegfr3 to modulate the proliferation of lymphatic endothelial cells through Ca2+ signaling[J]. Int J Biochem Cell Biol, 2018,102(9):51-58.
[8] Huang YCH, Huang XP, Zhu JY, et al. miR-128-3p suppresses hepatocellular carcinoma proliferation by regulating PIK3R1 and is correlated with the prognosis of HCC patients[J]. Oncol Rep, 2015, 33(6):2889-2898.
[9] Zhang R , Liu C , Niu Y , et al. MicroRNA-128-3p regulates mitomycin C-induced DNA damage response in lung cancer cells through repressing, SPTAN1[J]. Oncotarget, 2017, 8(35): 58098-58107.
[10]Zhao L, Li R, Xu S, et al. Tumor suppressor mir-128-3p inhibits metastasis and epithelial-mesenchymal transition by targeting zeb1 in esophageal squamous-cell cancer[J]. Acta Biochim Biophys Sin(Shanghai), 2018, 50(2): 171-180.
[11] Wang X, Wu G, Cao G, et al. Microrna335 inhibits bladder cancer cell growth and migration by targeting mitogenactivated protein kinase 1[J]. Mol Med Rep, 2016, 14(2): 1765-1770.
[12]Xu M, Li J, Wang X, et al. Mir-22 suppresses epithelial-mesenchymal transition in bladder cancer by inhibiting snail and mapk1/slug/vimentin feedback loop[J]. Cell Death Dis, 2018, 9(2): 209.
[13]Yu WW, Jiang H, Zhang CT, et al. The snail/mir-128 axis regulated growth, invasion, metastasis, and epithelial-to-mesenchymal transition of gastric cancer[J]. Oncotarget, 2017, 8(24): 39280-39295.
[14]Lin Y, Wu Z. Microrna-128 inhibits proliferation and invasion of glioma cells by targeting COX-2[J]. Gene, 2018, 658(5): 63-69.
[15]Zhou XU, Qi L, Tong S, et al. Mir-128 downregulation promotes growth and metastasis of bladder cancer cells and involves vegf-c upregulation [J]. Oncol Lett, 2015, 10(5): 3183-3190.
[16]Lin L, Chen X, Peng X, et al. Microrna-128 promotes cell-cell adhesion in u87 glioma cells via regulation of EphB2[J]. Oncol Rep, 2013, 30(3): 1239-1248.
[17]Song H, Tao Y, Ni N, et al. Mir-128 targets the cc chemokine ligand 18 gene(ccl18) in cutaneous malignant melanoma progression[J]. J Dermatol Sci, 2018, 91(3): 317-324.
[18]Labernadie A, Kato T, Brugués A, et al. A mechanically active heterotypic E-cadherin/N-cadherin adhesion enables fibroblasts to drive cancer cell invasion[J]. Nat Cell Biol, 2017, 19(3): 224-237.
[19] Wang W, Yi M, Zhang R, et al. Vimentin is a crucial target for anti-metastasis therapy of nasopharyngeal carcinoma[J]. Mol Cell Biochem, 2018, 438(1-2): 47-57.
[20]Jia S, Lu J, Qu T, et al. MAGI1 inhibits migration and invasion via blocking MAPK/ERK signaling pathway in gastric cancer[J]. Chin J Cancer Res, 2017, 29(1): 25-35.
[21] Delaney J, Chiarello R, Villar D, et al. Regulation of c-fos, c-jun and c-mycgene expression by angiotensin II in primary cultured rat astrocytes: role of ERK1/2 MAP kinases[J]. Neurochem Res, 2008, 33(3): 545-550.
