PMID- 30964170
OWN - NLM
STAT- MEDLINE
DCOM- 20200807
LR  - 20200807
IS  - 2284-0729 (Electronic)
IS  - 1128-3602 (Linking)
VI  - 23
IP  - 6
DP  - 2019 Mar
TI  - MiRNA-153-3p promotes gefitinib-sensitivity in non-small cell lung cancer by 
      inhibiting ATG5 expression and autophagy.
PG  - 2444-2452
LID - 17391 [pii]
LID - 10.26355/eurrev_201903_17391 [doi]
AB  - OBJECTIVE: To clarify the function of miRNA-153-3p in gefitinib-sensitive 
      non-small cell lung cancer (NSCLC) and the underlying mechanism. PATIENTS AND 
      METHODS: The expressions of miRNA-153-3p, LC3B and ATG5 in gefitinib-resistant 
      and gefitinib-sensitive NSCLC tissues were determined by quantitative Real 
      Time-Polymerase Chain Reaction (qRT-PCR). The correlation between miRNA-153-3p to 
      LC3B or ATG5 was analyzed. We evaluated autophagy level in gefitinib-resistant 
      NSCLC cells by calculating the percentage of PC-9/GR and HCC827/GR cells with 
      positive GFP-LC3, as well as determining autophagy-related gene levels. The 
      potential binding between ATG5 and miRNA-153-3p were verified by Dual-Luciferase 
      reporter gene assay. The regulatory effects of miRNA-153-3p/ATG5 on 
      gefitinib-sensitivity and apoptosis were finally examined by cytotoxicity assay 
      and Annexin V-fluorescein isothiocyanate (FITC)/Propidium Iodide (PI) staining, 
      respectively. RESULTS: MiRNA-153-3p was lowly expressed in gefitinib-resistant 
      NSCLC relative to the gefitinib-sensitive ones. MiRNA-153-3p was negatively 
      correlated with autophagy activity marker LC3B in gefitinib-resistant NSCLC 
      patients. Compared with parental cells, gefitinib-resistant NSCLC cell lines 
      PC-9/GR and HCC827/GR presented a lower level of miRNA-153-3p and a higher level 
      of autophagy. The overexpression of miRNA-153-3p greatly inhibited autophagy 
      level. ATG5 could directly bind to miRNA-153-3p, and ATG5 was highly expressed in 
      gefitinib-resistant NSCLC. The correlation analysis found a negative correlation 
      between ATG5 and miRNA-153-3p and a positive correlation between ATG5 and LC3B in 
      gefitinib-resistant NSCLC. More importantly, ATG5 reversed the regulatory effects 
      of miRNA-153-3p on autophagy, gefitinib-sensitivity and apoptosis of PC-9/GR and 
      HCC827/GR cells. CONCLUSIONS: MiRNA-153-3p is lowly expressed in 
      gefitinib-resistant NSCLC patients. The overexpression of miRNA-153-3p enhances 
      gefitinib-sensitivity in NSCLC by inhibiting autophagy via downregulating ATG5.
FAU - Zhang, W
AU  - Zhang W
AD  - Department of Thoracic Surgery, The Affiliated Yantai Yuhuangding Hospital of 
      Qingdao University, Yantai, China. yssqm12@sina.com.
FAU - Dong, Y-Z
AU  - Dong YZ
FAU - Du, X
AU  - Du X
FAU - Peng, X-N
AU  - Peng XN
FAU - Shen, Q-M
AU  - Shen QM
LA  - eng
PT  - Journal Article
PL  - Italy
TA  - Eur Rev Med Pharmacol Sci
JT  - European review for medical and pharmacological sciences
JID - 9717360
RN  - 0 (ATG5 protein, human)
RN  - 0 (Autophagy-Related Protein 5)
RN  - 0 (MAP1LC3B protein, human)
RN  - 0 (MIRN153 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (Microtubule-Associated Proteins)
RN  - S65743JHBS (Gefitinib)
SB  - IM
MH  - Autophagy/drug effects
MH  - Autophagy-Related Protein 5/*genetics/metabolism
MH  - Carcinoma, Non-Small-Cell Lung/*genetics/metabolism
MH  - Cell Line, Tumor
MH  - Cell Proliferation
MH  - Down-Regulation
MH  - Drug Resistance, Neoplasm
MH  - Gefitinib/*pharmacology
MH  - Humans
MH  - Lung Neoplasms/*genetics/metabolism
MH  - MicroRNAs/*genetics
MH  - Microtubule-Associated Proteins/metabolism
EDAT- 2019/04/10 06:00
MHDA- 2020/08/08 06:00
CRDT- 2019/04/10 06:00
PHST- 2019/04/10 06:00 [entrez]
PHST- 2019/04/10 06:00 [pubmed]
PHST- 2020/08/08 06:00 [medline]
AID - 17391 [pii]
AID - 10.26355/eurrev_201903_17391 [doi]
PST - ppublish
SO  - Eur Rev Med Pharmacol Sci. 2019 Mar;23(6):2444-2452. doi: 
      10.26355/eurrev_201903_17391.