PMID- 30439707
OWN - NLM
STAT- MEDLINE
DCOM- 20181211
LR  - 20190212
IS  - 1421-9778 (Electronic)
IS  - 1015-8987 (Linking)
VI  - 51
IP  - 1
DP  - 2018
TI  - Recovery of miR-139-5p in Ovarian Cancer Reverses Cisplatin Resistance by 
      Targeting C-Jun.
PG  - 129-141
LID - 10.1159/000495169 [doi]
AB  - BACKGROUND/AIMS: In platinum-based chemotherapy for ovarian cancer, acquired drug 
      resistance is a frequent occurrence. Because recent studies have demonstrated 
      that dysregulation of microRNAs (miRNAs) is partly responsible for the induction 
      of acquired drug resistance in cancers, we hypothesized that correcting the 
      dysregulation of key miRNAs would reverse the acquired resistance to 
      platinum-based drugs in ovarian cancer. METHODS: Cisplatin-resistant SKOV3 and 
      A2780 ovarian cancer cell lines (SKOV3-R and A2780-R, respectively) were 
      established by long-term exposure to cisplatin. MTT assays were performed to 
      evaluate the viability of SKOV3, SKOV3-R, A2780, and A2780-R cells. Quantitative 
      PCR was used to examine the expression of miR-139-5p in these cell lines. The 
      regulatory mechanism was confirmed by western blot analysis and luciferase 
      reporter assays. After treatment with miR-139-5p and cisplatin, mitochondrial 
      membrane potential and apoptosis were measured by using flow cytometry. 
      Interaction with c-Jun and activating transcription factor 2 (ATF2) was evaluated 
      by co-immunoprecipitation. Expression of B-cell lymphoma-extra large (Bcl-xl) and 
      activation of caspase-9 and caspase-3 were detected by western blotting. RESULTS: 
      Expression of miR-139-5p was decreased in SKOV3-R and A2780-R cells. Recovery of 
      miR-139-5p increased the sensitivity of SKOV3-R and A2780-R cells to cisplatin 
      treatment, inhibited the interaction of c-Jun and ATF2, and decreased Bcl-xl 
      expression in SKOV3-R and A2780-R cells. Expression of miR-139-5p promoted 
      cisplatin-induced mitochondrial apoptosis through binding the 3' untranslated 
      region of c-Jun mRNA. CONCLUSION: Recovery of miR-139-5p suppressed the 
      expression of c-Jun and thus reversed cisplatin-resistance in ovarian cancer.
CI  - (c) 2018 The Author(s). Published by S. Karger AG, Basel.
FAU - Jiang, Ying
AU  - Jiang Y
FAU - Jiang, Jing
AU  - Jiang J
FAU - Jia, Haiqing
AU  - Jia H
FAU - Qiao, Zhiwei
AU  - Qiao Z
FAU - Zhang, Jingru
AU  - Zhang J
LA  - eng
PT  - Journal Article
DEP - 20181115
PL  - Germany
TA  - Cell Physiol Biochem
JT  - Cellular physiology and biochemistry : international journal of experimental 
      cellular physiology, biochemistry, and pharmacology
JID - 9113221
RN  - 0 (3' Untranslated Regions)
RN  - 0 (ATF2 protein, human)
RN  - 0 (Activating Transcription Factor 2)
RN  - 0 (Antagomirs)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (MIRN139 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (bcl-X Protein)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - 3' Untranslated Regions
MH  - Activating Transcription Factor 2/metabolism
MH  - Animals
MH  - Antagomirs/metabolism
MH  - Antineoplastic Agents/*pharmacology/therapeutic use
MH  - Apoptosis/*drug effects
MH  - Cell Line, Tumor
MH  - Cisplatin/*pharmacology/therapeutic use
MH  - Drug Resistance, Neoplasm
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & 
      inhibitors/genetics/*metabolism
MH  - Mice
MH  - Mice, Nude
MH  - MicroRNAs/antagonists & inhibitors/genetics/*metabolism
MH  - Ovarian Neoplasms/drug therapy/pathology
MH  - RNA Interference
MH  - RNA, Small Interfering/metabolism
MH  - bcl-X Protein/metabolism
OTO - NOTNLM
OT  - C-Jun
OT  - Cisplatin
OT  - Ovarian cancer
OT  - miR-139-5p
EDAT- 2018/11/16 06:00
MHDA- 2018/12/12 06:00
CRDT- 2018/11/16 06:00
PHST- 2018/03/13 00:00 [received]
PHST- 2018/11/07 00:00 [accepted]
PHST- 2018/11/16 06:00 [pubmed]
PHST- 2018/12/12 06:00 [medline]
PHST- 2018/11/16 06:00 [entrez]
AID - 000495169 [pii]
AID - 10.1159/000495169 [doi]
PST - ppublish
SO  - Cell Physiol Biochem. 2018;51(1):129-141. doi: 10.1159/000495169. Epub 2018 Nov 
      15.