Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer

被引:58
作者
Gu, Yuanyuan [1 ]
Liu, Shuoxin [2 ]
Zhang, Xiaodan [1 ]
Chen, Guimin [2 ]
Liang, Hongwei [1 ]
Yu, Mengchao [1 ]
Liao, Zhicong [3 ,4 ]
Zhou, Yong [3 ,4 ]
Zhang, Chen-Yu [1 ]
Wang, Tao [1 ]
Wang, Chen [1 ]
Zhang, Junfeng [1 ]
Chen, Xi [1 ]
机构
[1] Nanjing Univ, Sch Life Sci, Jiangsu Engn Res Ctr Micro RNA Biol & Biotechnol, NJU Adv Inst Life Sci NAILS,State Key Lab Pharmac, Nanjing 210046, Jiangsu, Peoples R China
[2] Linyi Tumor Hosp, Dept Med Oncol 2, Linyi 276000, Peoples R China
[3] Nanjing Univ, Nanjing Drum Tower Hosp, Med Sch, Dept Cardiothorac Surg, Nanjing 210008, Jiangsu, Peoples R China
[4] Nanjing Multictr Biobank, Nanjing 210008, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
microRNA; MTUS1; miR-19a/b; lung cancer; proliferation; migration; DOWN-REGULATION; POOR-PROGNOSIS; AT2; RECEPTOR; MICRORNAS; EXPRESSION; IDENTIFICATION; MIR-17-92; PROTEIN; GROWTH;
D O I
10.1007/s13238-017-0393-7
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
MTUS1 (microtubule-associated tumor suppressor 1) has been identified that can function as a tumor suppressor gene in many malignant tumors. However, the function and mechanisms underlying the regulation of MTUS1 are unclear. In the present study, we reported that miR-19a and miR-19b (miR-19a/b) promote proliferation and migration of lung cancer cells by targeting MTUS1. First, MTUS1 was proved to function as a tumor suppressor in lung cancer and was linked to cell proliferation and migration promotion. Second, an inverse correlation between miR-19a/b expression and MTUS1 mRNA/protein expression was noted in human lung cancer tissues. Third, MTUS1 was appraised as a direct target of miR-19a/b by bioinformatics analysis. Fourth, direct MTUS1 regulation by miR-19a/b in lung cancer cells was experimentally affirmed by cell transfection assay and luciferase reporter assay. Finally, miR-19a/b were shown to cooperatively repress MTUS1 expression and synergistically regulate MTUS1 expression to promote lung cancer cell proliferation and migration. In conclusion, our findings have provided the first clues regarding the roles of miR-19a/b, which appear to function as oncomirs in lung cancer by downregulating MTUS1.
引用
收藏
页码:455 / 466
页数:12
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