Elevated microRNA-130b-5p or silenced ELK1 inhibits self-renewal ability, proliferation, migration, and invasion abilities, and promotes apoptosis of cervical cancer stem cells

被引:10
作者
Huang, Yu [1 ,2 ]
Luo, Fangyuan [1 ,2 ]
机构
[1] Sichuan Acad Med Sci, 32 West Second Sect,First Ring Rd, Chengdu 610072, Peoples R China
[2] Sichuan Prov Peoples Hosp, 32 West Second Sect,First Ring Rd, Chengdu 610072, Peoples R China
关键词
apoptosis; cervical cancer; colony formation; ELK1; invasion; MicroRNA‐ 130b‐ 5p; migration; proliferation; self‐ renewal ability; stem cells; stemness; DOWN-REGULATION; TUMORIGENESIS; EXPRESSION; PROGNOSIS; OCT4; METASTASIS; ANDROGEN; WOMEN; SOX2;
D O I
10.1002/iub.2409
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cervical cancer (CC) is the most familiar gynecological malignancy. With the poor prognosis of CC patients, this study explored the effect of microRNA (miR)-130b-5p targeting ELK1 expression on self-renewal ability and stemness of CC stem cells. The tissues of patients with CC or cervical benign lesions were collected. MiR-130b-5p and ELK1 expression was detected by reverse transcription quantitative polymerase chain reaction and western blot analysis. Human CC cell line Hela was cultured and the induced CC stem cells were introduced with miR-130b-5p mimic or silenced ELK1 to figure their roles in self-renewal ability, stemness, colony formation, proliferation, migration, invasion abilities, and apoptosis of CC stem cells. Tumor growth was detected in nude mice in vivo. The targeting relationship between miR-130b-5p and ELK1 was analyzed using bioinformatic prediction and dual luciferase reporter gene assay. Decreased miR-130b-5p and elevated ELK1 existed in CC tissues of patients. Up-regulated miR-130b-5p decreased ELK1 expression in CC stem cells. Elevated miR-130b-5p or silenced ELK1 inhibited self-renewal ability and stemness, colony formation, proliferation, migration and invasion abilities, promoted apoptosis of CC stem cells, as well as decreased the weight and volume of tumor in nude mice. ELK1 was found to be targeted by miR-130b-5p. Overexpression ELK1 effectively reversed the cellular phenotypic changes and tumor formation in vivo caused by up-regulation of miR-130b-5p. We conclude that up-regulated miR-130b-5p or silenced ELK1 inhibits CC stem cell growth.
引用
收藏
页码:118 / 129
页数:12
相关论文
共 28 条
[1]   MiR-130b suppresses prostate cancer metastasis through down-regulation of MMP2 [J].
Chen, Qin ;
Zhao, Xian ;
Zhang, Hailong ;
Yuan, Haihua ;
Zhu, Miaojun ;
Sun, Qian ;
Lai, Xueping ;
Wang, Yanli ;
Huang, Jian ;
Yan, Jianshe ;
Yu, Jianxiu .
MOLECULAR CARCINOGENESIS, 2015, 54 (11) :1292-1300
[2]   CD36 promotes the epithelial-mesenchymal transition and metastasis in cervical cancer by interacting with TGF-β [J].
Deng, Min ;
Cai, Xiaodong ;
Long, Ling ;
Xie, Linying ;
Ma, Hongmei ;
Zhou, Youjian ;
Liu, Shuguang ;
Zeng, Chao .
JOURNAL OF TRANSLATIONAL MEDICINE, 2019, 17 (01)
[3]   Downregulation of miR-146a promotes tumorigenesis of cervical cancer stem cells via VEGF/CDC42/PAK1 signaling pathway [J].
Dong, Zhihong ;
Yu, Chunxia ;
Rezhiya, Kuerban ;
Gulijiahan, Aier ;
Wang, Xinling .
ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY, 2019, 47 (01) :3711-3719
[4]   Prevalence of human papillomavirus infection, cervical intraepithelial neoplasia and cervical cancer in imprisoned women worldwide: a systematic review and meta-analysis [J].
Escobar, Nadia ;
Plugge, Emma .
JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH, 2020, 74 (01) :95-102
[5]   MiR-185-5p suppresses HBV gene expression by targeting ELK1 in hepatoma carcinoma cells [J].
Fan, Hong-Xia ;
Feng, Yu-Jie ;
Zhao, Xiao-Pei ;
He, Yu-Ze ;
Tang, Hua .
LIFE SCIENCES, 2018, 213 :9-17
[6]   Gene regulation by antitumor miR-130b-5p in pancreatic ductal adenocarcinoma: the clinical significance of oncogenic EPS8 [J].
Fukuhisa, Haruhi ;
Seki, Naohiko ;
Idichi, Tetsuya ;
Kurahara, Hiroshi ;
Yamada, Yasutaka ;
Toda, Hiroko ;
Kita, Yoshiaki ;
Kawasaki, Yota ;
Tanoue, Kiyonori ;
Mataki, Yuko ;
Maemura, Kosei ;
Natsugoe, Shoji .
JOURNAL OF HUMAN GENETICS, 2019, 64 (06) :521-534
[7]   Prognostic significance of low DICER expression regulated by miR-130a in cervical cancer [J].
He, L. ;
Wang, H-Y ;
Zhang, L. ;
Huang, L. ;
Li, J-D ;
Xiong, Y. ;
Zhang, M-Y ;
Jia, W-H ;
Yun, J-P ;
Luo, R-Z ;
Zheng, M. .
CELL DEATH & DISEASE, 2014, 5 :e1205-e1205
[8]   ELK1-activated GPC3-AS1/GPC3 axis promotes the proliferation and migration of cervical cancer cells [J].
Hu, Rong ;
Zhu, Zongming .
JOURNAL OF GENE MEDICINE, 2019, 21 (08)
[9]  
Inoue S, 2018, AM J CANCER RES, V8, P2325
[10]  
Ji J, 2014, INT J CLIN EXP PATHO, V7, P2470