NEAT1 regulates cell proliferation and apoptosis of ovarian cancer by miR-34a-5p/BCL2

被引:108
作者
Ding, Nan [1 ]
Wu, Haiying [1 ]
Tao, Tao [1 ]
Peng, Erxuan [2 ]
机构
[1] Henan Prov Peoples Hosp, Dept Obstet & Gynecol, 3 Weiwu Rd, Zhengzhou 450003, Henan, Peoples R China
[2] Henan Prov Tumor Hosp, Dept Obstet & Gynecol, Zhengzhou, Henan, Peoples R China
关键词
NEAT1; miR-34a-5p; BCL2; ovarian cancer; caspase-3; ceRNA; LONG NONCODING RNA; LNCRNA NEAT1; PROGRESSION; INVASION; BLADDER;
D O I
10.2147/OTT.S142446
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
Background: Nuclear enriched abundant transcript 1 (NEAT1) has been demonstrated to act as a tumor inhibitor in many cancers. However, the role of NEAT1 in the development of ovarian cancer (OC) remains far from being elaborated. Hence, the aim of this study is to investigate the expression and function of NEAT1 in OC. Materials and methods: The expression level of NEAT1 was determined by quantitative real-time polymerase chain reaction in OC cell lines. MTT assay, caspase-3 activity assay, and flow cytometry analysis were conducted to investigate the effects of NEAT1, miR-34a-5p, or B-cell lymphoma-2 (BCL2) on OC cell proliferation and apoptosis. Luciferase reporter assay was used to confirm the interaction of NEAT1, BCL2, and miR-34a-5p in OC cells. Results: NEAT1 was significantly upregulated in OC cell lines. NEAT1 overexpression promoted proliferation by increasing the proportion of cells in S phase and suppressed apoptosis of OC cells, while knockdown of NEAT1 had the opposite effect. In addition, NEAT1 was demonstrated to directly interact with miR- 34a-5p and exert its oncogenic role in OC by negatively regulating miR-34a-5p. Moreover, miR-34a-5p could directly target BCL2 and suppressed its expression. miR- 34a-5p overexpression suppressed OC cell proliferation and triggered apoptosis by targeting BCL2. Furthermore, NEAT1 knockdown suppressed BCL2 expression, while anti-miR-34a-5p dramatically abated the inhibitory effect of si-NEAT1 on BCL2 expression. Conclusion: NEAT1 regulated proliferation and apoptosis of OC cells by miR-34a-5p/BCL2, providing a potential therapeutic approach for the treatment of OC patients.
引用
收藏
页码:4905 / 4915
页数:11
相关论文
共 31 条
[1]
[Anonymous], 2018, ANTI-CANCER DRUG, DOI [DOI 10.3322/caac.20115, DOI 10.1097/CAD.0000000000000617]
[2]
HuR-regulated lncRNA NEAT1 stability in tumorigenesis and progression of ovarian cancer [J].
Chai, Yiqing ;
Liu, Jie ;
Zhang, Zhikun ;
Liu, Liwei .
CANCER MEDICINE, 2016, 5 (07) :1588-1598
[3]
Chen XJ, 2015, AM J CANCER RES, V5, P2808
[4]
Chen ZJ, 2016, EUR REV MED PHARMACO, V20, P3373
[5]
A long noncoding RNA AB073614 promotes tumorigenesis and predicts poor prognosis in ovarian cancer [J].
Cheng, Zhongping ;
Guo, Jing ;
Chen, Li ;
Luo, Ning ;
Yang, Weihong ;
Qu, Xiaoyan .
ONCOTARGET, 2015, 6 (28) :25381-25389
[6]
An Architectural Role for a Nuclear Noncoding RNA: NEAT1 RNA Is Essential for the Structure of Paraspeckles [J].
Clemson, Christine M. ;
Hutchinson, John N. ;
Sara, Sergio A. ;
Ensminger, Alexander W. ;
Fox, Archa H. ;
Chess, Andrew ;
Lawrence, Jeanne B. .
MOLECULAR CELL, 2009, 33 (06) :717-726
[7]
CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism [J].
Ellis, Blake C. ;
Graham, Lloyd D. ;
Molloy, Peter L. .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH, 2014, 1843 (02) :372-386
[8]
Oncocers: ceRNA-mediated cross-talk by sponging miRNAs in oncogenic pathways [J].
Ergun, Sercan ;
Oztuzcu, Serdar .
TUMOR BIOLOGY, 2015, 36 (05) :3129-3136
[9]
MiR-34a Inhibits Viability and Invasion of Human Papillomavirus-Positive Cervical Cancer Cells by Targeting E2F3 and Regulating Survivin [J].
Geng, Dianzhong ;
Song, Xiaohua ;
Ning, Fangling ;
Song, Qianhua ;
Yin, Honghua .
INTERNATIONAL JOURNAL OF GYNECOLOGICAL CANCER, 2015, 25 (04) :707-713
[10]
The functional role of long non-coding RNA in human carcinomas [J].
Gibb, Ewan A. ;
Brown, Carolyn J. ;
Lam, Wan L. .
MOLECULAR CANCER, 2011, 10