PMID- 31913198
OWN - NLM
STAT- MEDLINE
DCOM- 20210202
LR  - 20211204
IS  - 1473-5741 (Electronic)
IS  - 0959-4973 (Linking)
VI  - 31
IP  - 4
DP  - 2020 Apr
TI  - miR-21 modulates cisplatin resistance of gastric cancer cells by inhibiting 
      autophagy via the PI3K/Akt/mTOR pathway.
PG  - 385-393
LID - 10.1097/CAD.0000000000000886 [doi]
AB  - Resistance to cisplatin (DDP) remains a major obstacle in the control of gastric 
      cancer (GC) progression. A previous study revealed that microRNA-21 (miR-21) 
      contributes to DDP resistance in GC cells via the phosphoinositide 3-kinase 
      (PI3K)/protein kinase B (Akt) pathway. The aim of the current study was to 
      explore the mechanisms underlying the cytoprotective function of miR-21. In this 
      study, DDP-resistant GC cells were obtained by continuous exposure of human 
      gastric adenocarcinoma cells to increasing concentrations of DDP. Western blot 
      analysis was used to evaluate activation of the PI3K/Akt/mechanistic target of 
      rapamycin kinase (mTOR) pathway. The level of miR-21 was altered by transfection 
      of miR-21 mimic and inhibitor. Autophagy was assessed by detecting autophagosome 
      formation, Beclin-1 and LC3 expression. An Annexin V-propidium iodide assay was 
      performed to estimate the survival and death of GC cells. GC cells became 
      refractory to the growth inhibition and apoptosis induced by DDP treatment, 
      activation of Akt and mTOR were increased in DDP-resistant GC cells. Inhibition 
      of autophagy decreased the sensitivity of GC cells to DDP, and autophagy 
      induction produced the opposite effect. DDP-resistant GC cells expressed higher 
      levels of miR-21 compared with the parent cells. Transfection of GC cells with 
      miR-21 mimics contributed to restored DDP resistance by suppressing autophagy, 
      while miR-21 inhibitor sensitized DDP-resistant GC cells by promoting autophagy. 
      In conclusion, the results demonstrated that miR-21 is associated with DDP 
      resistance in GC cells by inhibiting autophagy via the PI3K/Akt/mTOR pathway, and 
      autophagy inducers could be therapeutic targets for the effective treatment of 
      DDP resistance in GC.
FAU - Gu, Yifan
AU  - Gu Y
AD  - Department of General Surgery, Xinhua Hospital, School of Medicine.
FAU - Fei, Zhewei
AU  - Fei Z
AD  - Department of General Surgery, Xinhua Hospital, School of Medicine.
AD  - Department of General Surgery, Xinhua Hospital Chongming Branch, School of 
      Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
FAU - Zhu, Ronghua
AU  - Zhu R
AD  - Department of General Surgery, Xinhua Hospital Chongming Branch, School of 
      Medicine, Shanghai Jiaotong University, Shanghai, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Anticancer Drugs
JT  - Anti-cancer drugs
JID - 9100823
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (MIRN21 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (AKT1 protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis
MH  - *Autophagy
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Cell Proliferation
MH  - Cisplatin/pharmacology
MH  - Drug Resistance, Neoplasm/*genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - Phosphatidylinositol 3-Kinases/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - Signal Transduction/drug effects
MH  - Stomach Neoplasms/*drug therapy/genetics/metabolism/pathology
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2020/01/09 06:00
MHDA- 2021/02/03 06:00
CRDT- 2020/01/09 06:00
PHST- 2020/01/09 06:00 [pubmed]
PHST- 2021/02/03 06:00 [medline]
PHST- 2020/01/09 06:00 [entrez]
AID - 00001813-202004000-00009 [pii]
AID - 10.1097/CAD.0000000000000886 [doi]
PST - ppublish
SO  - Anticancer Drugs. 2020 Apr;31(4):385-393. doi: 10.1097/CAD.0000000000000886.