PMID- 29098549
OWN - NLM
STAT- MEDLINE
DCOM- 20171205
LR  - 20211204
IS  - 1573-2568 (Electronic)
IS  - 0163-2116 (Linking)
VI  - 62
IP  - 12
DP  - 2017 Dec
TI  - The GAS5/miR-222 Axis Regulates Proliferation of Gastric Cancer Cells Through the 
      PTEN/Akt/mTOR Pathway.
PG  - 3426-3437
LID - 10.1007/s10620-017-4831-4 [doi]
AB  - BACKGROUND: Several lines of evidence have indicated that growth arrest-specific 
      transcript 5 (GAS5) functions as a tumor suppressor and is aberrantly expressed 
      in multiple cancers. GAS5 was found to be downregulated in gastric cancer (GC) 
      tissues, and ectopic expression of GAS5 inhibited GC cell proliferation. AIMS: 
      The present study aimed to explore the underlying mechanisms of GAS5 involved in 
      GC cell proliferation. METHODS: GAS5 and miR-222 expressions in GC cell lines 
      were estimated by quantitative real-time polymerase chain reaction. The effects 
      of GAS5 and miR-222 on GC cell proliferation were assessed by MTT assay and 
      5-bromo-2-deoxyuridine (BrdU) incorporation assays. The interaction between GAS5 
      and miR-222 was confirmed by luciferase reporter assay and RNA 
      immunoprecipitation assay. The protein levels of the phosphatase and tensin 
      homolog (PTEN), phosphorylated protein kinase B (Akt) (p-Akt), Akt, 
      phosphorylated mammalian target of rapamycin (mTOR) (p-mTOR), and mTOR were 
      determined by western blot. RESULTS: GAS5 was downregulated and miR-222 was 
      upregulated in GC cells. GAS5 directly targeted and suppressed miR-222 
      expression. GAS5 overexpression and miR-222 inhibition suppressed cell 
      proliferation, increased PTEN protein level and decreased p-Akt and p-mTOR 
      protein levels in GC cells while GAS5 knockdown and miR-222 overexpression 
      exhibited the opposite effects. Moreover, mechanistic analyses revealed that GAS5 
      regulated GC cell proliferation through the PTEN/Akt/mTOR pathway by negatively 
      regulating miR-222. CONCLUSIONS: GAS5/miR-222 axis regulated proliferation of GC 
      cells through the PTEN/Akt/mTOR pathway, which facilitated the development of 
      lncRNA-directed therapy against this deadly disease.
FAU - Li, Yanhua
AU  - Li Y
AD  - Department of Oncology, Huaihe Hospital of Henan University, No. 8 Baobei Road, 
      Kaifeng, 475000, Henan, People's Republic of China.
FAU - Gu, Junjiao
AU  - Gu J
AD  - Department of Oncology, Huaihe Hospital of Henan University, No. 8 Baobei Road, 
      Kaifeng, 475000, Henan, People's Republic of China.
FAU - Lu, Hong
AU  - Lu H
AD  - Department of Oncology, Huaihe Hospital of Henan University, No. 8 Baobei Road, 
      Kaifeng, 475000, Henan, People's Republic of China. honglu6512@163.com.
LA  - eng
GR  - 9412016Y1403/Science & Technology Department of Henan Province/International
PT  - Journal Article
DEP - 20171102
PL  - United States
TA  - Dig Dis Sci
JT  - Digestive diseases and sciences
JID - 7902782
RN  - 0 (GAS5 long non-coding RNA, human)
RN  - 0 (MIRN22 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Long Noncoding)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (PTEN protein, human)
SB  - IM
MH  - Cell Line, Tumor
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - MicroRNAs/*metabolism
MH  - PTEN Phosphohydrolase/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Long Noncoding/*metabolism
MH  - Stomach Neoplasms/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
OTO - NOTNLM
OT  - GAS5
OT  - Gastric cancer
OT  - PTEN/Akt/mTOR pathway
OT  - Proliferation
OT  - miR-222
EDAT- 2017/11/04 06:00
MHDA- 2017/12/06 06:00
CRDT- 2017/11/04 06:00
PHST- 2017/07/27 00:00 [received]
PHST- 2017/10/25 00:00 [accepted]
PHST- 2017/11/04 06:00 [pubmed]
PHST- 2017/12/06 06:00 [medline]
PHST- 2017/11/04 06:00 [entrez]
AID - 10.1007/s10620-017-4831-4 [pii]
AID - 10.1007/s10620-017-4831-4 [doi]
PST - ppublish
SO  - Dig Dis Sci. 2017 Dec;62(12):3426-3437. doi: 10.1007/s10620-017-4831-4. Epub 2017 
      Nov 2.