Effects of miR-490-5p targeting CDK1 on proliferation and apoptosis of colon cancer cells via ERK signaling pathway

被引:3
作者
Yang, Y-J [1 ]
Luo, S. [1 ]
Xu, Z-L [1 ]
机构
[1] Jinan Univ, Shenzhen Peoples Hosp, Dept Gastroenterol, Clin Med Coll 2, Shenzhen, Peoples R China
关键词
MiR-490-5p; Colon cancer; Proliferation; Apoptosis; CDK1; MICRORNA; CARCINOMA; GROWTH;
D O I
暂无
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
OBJECTIVE: The aim of this study was to investigate the effects of micro ribonucleic acid (miR)-490-5p on the proliferation and apoptosis of colon cancer cells, and to explore its potential mechanism. PATIENTS AND METHODS: The mRNA expression of miR-490-5p in 30 pairs of colon cancer tissues and adjacent normal tissues was detected via reverse transcription-polymerase chain reaction (RT-PCR). Human colon cancer SW480 cell lines were cultured in vitro and divided into Control group and miR-490-5p overexpression group (miR-490-5p mimic group). The nonsense sequence and miR-490-5p mimic were transfected using liposome transfection technique into colon cancer cells in control group and miR-490-5p mimic group, respectively. Cell proliferation and apoptosis in each group were then observed. At the same time, the effect of miR-490-5p on the growth of colon cancer in vivo was explored using subcutaneous tumorigenesis assay. The protein expressions of extracellular signal-regulated kinase (ERK)1/2 signaling pathway and cyclin-dependent kinase 1 (CDK1) were determined via Western blotting. Furthermore, immunohistochemical staining was performed to verify the protein expression of CDK1 in vivo. RESULTS: The expression of miR-490-5p in colon cancer tissues was significantly lower than that in adjacent normal tissues (p<0.05). After transfection with miR-490-5p mimic in vitro. EdU staining and colony formation assay showed that the proliferation ability of SW480 cells was significantly weakened (p<0.05). Meanwhile, the number of colonies in miR-490-5p mimic group was markedly less than that in Control group (p<0.05). The results of Western blotting revealed that overexpression of miR-490-5p remarkably up-regulated the Bax/Bcl-2 and C-Caspase3/T-Caspase3 ratios in cancer cells (p<0.05). Subsequent results indicated that the subcutaneous tumorigenesis of colon cancer cells was markedly inhibited by overexpression of miR-490-5p (p<0.05). According to the results of Western blotting. the activation of ERK signaling pathway and the protein expression of CDK1 were significantly suppressed by overexpression of miR-490-5p (p<0.05). In vivo experiments further revealed that the protein expression of CDK1 in colon cancer tissues increased significantly (p<0.05). CONCLUSIONS: MiR-490-5p was found lowly expressed in colon cancer patients. In addition. overexpression of miR-490-5p inhibited the proliferation and promoted the apoptosis of colon cancer cells via down-regulating CDK1 both in vitro and in vivo.
引用
收藏
页码:2049 / 2056
页数:8
相关论文
共 24 条
[1]   Dose-response effects of aerobic exercise on body composition among colon cancer survivors: a randomised controlled trial [J].
Brown, Justin C. ;
Zemel, Babette S. ;
Troxel, Andrea B. ;
Rickels, Michael R. ;
Damjanov, Nevena ;
Ky, Bonnie ;
Rhim, Andrew D. ;
Rustgi, Anil K. ;
Courneya, Kerry S. ;
Schmitz, Kathryn H. .
BRITISH JOURNAL OF CANCER, 2017, 117 (11) :1614-1620
[2]   MicroRNA-cancer connection: The beginning of a new tale [J].
Calin, George Adrian ;
Croce, Carlo Maria .
CANCER RESEARCH, 2006, 66 (15) :7390-7394
[3]   miR-490-5p suppresses tumour growth in renal cell carcinoma through targeting PIK3CA [J].
Chen, Ke ;
Zeng, Jin ;
Tang, Kun ;
Xiao, Haibing ;
Hu, Junhui ;
Huang, Chunhua ;
Yao, Weimin ;
Yu, Gan ;
Xiao, Wei ;
Guan, Wei ;
Guo, Xiaolin ;
Xu, Hua ;
Ye, Zhangqun .
BIOLOGY OF THE CELL, 2016, 108 (02) :41-50
[4]   MicroRNA-490-3P targets CDK1 and inhibits ovarian epithelial carcinoma tumorigenesis and progression [J].
Chen, Shuo ;
Chen, Xi ;
Xiu, Yin-Ling ;
Sun, Kai-Xuan ;
Zhao, Yang .
CANCER LETTERS, 2015, 362 (01) :122-130
[5]   MiR-490-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Migration and Invasion by Directly Regulating ROBO1 [J].
Chen, Weiqing ;
Ye, Lijun ;
Wen, Dengcheng ;
Chen, Feihua .
PATHOLOGY & ONCOLOGY RESEARCH, 2019, 25 (01) :1-9
[6]  
Fang H, 2017, AM J TRANSL RES, V9, P953
[7]  
Ichimura K, 2002, TRENDS PLANT SCI, V7, P301, DOI 10.1016/S1360-1385(02)02302-6
[8]   miR-17-5p suppresses cell proliferation and invasion by targeting ETV1 in triple-negative breast cancer [J].
Li, Jie ;
Lai, Yuanhui ;
Ma, Jieyi ;
Liu, Yue ;
Bi, Jiong ;
Zhang, Longjuan ;
Chen, Lianzhou ;
Yao, Chen ;
Lv, Weiming ;
Chang, Guangqi ;
Wang, Shenming ;
Ouyang, Mao ;
Wang, Wenjian .
BMC CANCER, 2017, 17
[9]   INACTIVATION OF THE TYPE-II TGF-BETA RECEPTOR IN COLON-CANCER CELLS WITH MICROSATELLITE INSTABILITY [J].
MARKOWITZ, S ;
WANG, J ;
MYEROFF, L ;
PARSONS, R ;
SUN, LZ ;
LUTTERBAUGH, J ;
FAN, RS ;
ZBOROWSKA, E ;
KINZLER, KW ;
VOGELSTEIN, B ;
BRATTAIN, M ;
WILLSON, JKV .
SCIENCE, 1995, 268 (5215) :1336-1338
[10]   MiR-1 Downregulation Cooperates with MACC1 in Promoting MET Overexpression in Human Colon Cancer [J].
Migliore, Cristina ;
Martin, Valentina ;
Leoni, Vera P. ;
Restivo, Angelo ;
Atzori, Luigi ;
Petrelli, Annalisa ;
Isella, Claudio ;
Zorcolo, Luigi ;
Sarotto, Ivana ;
Casula, Giuseppe ;
Comoglio, Paolo M. ;
Columbano, Amedeo ;
Giordano, Silvia .
CLINICAL CANCER RESEARCH, 2012, 18 (03) :737-747