PMID- 27875524
DCOM- 20170613
LR  - 20180214
IS  - 1532-1827 (Electronic)
IS  - 0007-0920 (Linking)
VI  - 116
IP  - 1
DP  - 2017 Jan 3
TI  - microRNA-137 promotes apoptosis in ovarian cancer cells via the regulation of
PG  - 66-76
LID - 10.1038/bjc.2016.379 [doi]
AB  - BACKGROUND: microRNAs (miRNAs) have regulatory roles in various cellular
      processes, including apoptosis. Recently, X-linked inhibitor of apoptosis protein
      (XIAP) has been reported to be dysregulated in epithelial ovarian cancer (EOC).
      However, the mechanism underlying this dysregulation is largely unknown. METHODS:
      Using bioinformatics and a literature analysis, a panel of miRNAs dysregulated in
      EOC was chosen for further experimental confirmation from hundreds of miRNAs that
      were predicted to interact with the XIAP 3'UTR. A dual-luciferase reporter assay 
      was employed to detect the interaction by cellular co-transfection of an miRNA
      expression vector and a reporter vector with the XIAP 3'UTR fused to a Renilla
      luciferase reporter. DAPI and TUNEL approaches were used to further determine the
      effects of an miR-137 mimic and inhibitor on cisplatin-induced apoptosis in
      ovarian cancer cells. RESULTS: We identified eight miRNAs by screening a panel of
      dysregulated miRNAs that may target the XIAP 3'UTR. The strongest inhibitory
      miRNA, miR-137, suppressed the activity of a luciferase reporter gene fused with 
      the XIAP 3'UTR and decreased the levels of XIAP protein in SKOV3 ovarian cancer
      cells. Furthermore, forced expression of miR-137 increased cisplatin-induced
      apoptosis, and the depressed expression of miR-137 decreased cisplatin-induced
      apoptosis in SKOV3 and primary EOC cells. Consistently, the disruption of miR-137
      via CRISPR/Cas9 inhibited apoptosis and upregulated XIAP in A2780 cells.
      Furthermore, the effect of miR-137 on apoptosis could be rescued by XIAP in SKOV3
      cells. In addition, miR-137 expression is inversely correlated with the level of 
      XIAP protein in both ovarian cancer tissues and cell lines. CONCLUSIONS: Our data
      suggest that multiple miRNAs can regulate XIAP via its 3'UTR. miR-137 can
      sensitise ovarian cancer cells to cisplatin-induced apoptosis, providing new
      insight into overcoming drug resistance in ovarian cancer.
FAU - Li, Xiaodi
AU  - Li X
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen
      University, Guangzhou, China.
FAU - Chen, Wei
AU  - Chen W
AD  - Department of Gynecology, The Second Affiliated Hospital of Guangzhou Medical
      University, Guangzhou, China.
FAU - Zeng, Wenshu
AU  - Zeng W
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen
      University, Guangzhou, China.
FAU - Wan, Chunling
AU  - Wan C
AD  - Bio-X Institutes, Key Laboratory for the Genetics of Developmental and
      Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong
      University, Shanghai, China.
FAU - Duan, Shiwei
AU  - Duan S
AD  - Medical Genetics Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 
      315211, China.
FAU - Jiang, Songshan
AU  - Jiang S
AD  - State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen
      University, Guangzhou, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161122
PL  - England
TA  - Br J Cancer
JT  - British journal of cancer
JID - 0370635
RN  - 0 (3' Untranslated Regions)
RN  - 0 (MIRN137 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (X-Linked Inhibitor of Apoptosis Protein)
RN  - 0 (XIAP protein, human)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Apoptosis/*genetics
MH  - Cell Line, Tumor
MH  - Drug Resistance, Neoplasm/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - HEK293 Cells
MH  - Humans
MH  - MicroRNAs/*physiology
MH  - Ovarian Neoplasms/genetics/*pathology
MH  - X-Linked Inhibitor of Apoptosis Protein/*genetics
PMC - PMC5220146
EDAT- 2016/11/23 06:00
MHDA- 2017/06/14 06:00
CRDT- 2016/11/23 06:00
PHST- 2016/06/10 00:00 [received]
PHST- 2016/09/28 00:00 [revised]
PHST- 2016/10/21 00:00 [accepted]
PHST- 2016/11/23 06:00 [pubmed]
PHST- 2017/06/14 06:00 [medline]
PHST- 2016/11/23 06:00 [entrez]
AID - bjc2016379 [pii]
AID - 10.1038/bjc.2016.379 [doi]
PST - ppublish
SO  - Br J Cancer. 2017 Jan 3;116(1):66-76. doi: 10.1038/bjc.2016.379. Epub 2016 Nov