PMID- 32240637
OWN - NLM
STAT- MEDLINE
DCOM- 20200713
LR  - 20211204
IS  - 1096-0384 (Electronic)
IS  - 0003-9861 (Linking)
VI  - 685
DP  - 2020 May 30
TI  - Rab1A knockdown represses proliferation and promotes apoptosis in gastric cancer 
      cells by inhibition of mTOR/p70S6K pathway.
PG  - 108352
LID - S0003-9861(20)30070-9 [pii]
LID - 10.1016/j.abb.2020.108352 [doi]
AB  - Rab1A, a member of the Ras-like protein in rat brain (Rab) family, acts as an 
      oncogene in a variety of malignant tumors. Previous studies reported that Rab1A 
      was highly expressed in GC tissues. However, the function and molecular mechanism 
      of Rab1A in gastric cancer (GC) development remain far from being addressed. 
      Rab1A mRNA and protein levels were detected by qRT-PCR and western blot, 
      respectively. Cell proliferation was evaluated by CCK-8 and BrdU incorporation 
      assays. Apoptosis was estimated by flow cytometry analysis and western blot 
      analysis of B cell lymphoma 2 (Bcl-2), myeloid cell leukemia 1 (Mcl-1), Bcl-2 
      associated X (Bax), and Bcl-2 homologous antagonist/killer (Bak) expression. 
      Alteration of the mammalian target of rapamycin (mTOR)/p70 ribosomal protein S6 
      kinase (p70S6K) signaling pathway was detected by western blot. We found that 
      Rab1A expression at both mRNA and protein was upregulated in GC cells. Rab1A 
      knockdown significantly inhibited cell proliferation and induced apoptosis in GC 
      cells. Rab1A overexpression promoted proliferation, inhibited cisplatin-induced 
      apoptosis, and increased xenograft growth. In addition, we found that Rab1A 
      knockdown suppressed the mTOR/p70S6K pathway in GC cells. Moreover, activation of 
      mTOR/p70S6K pathway by MHY1485 abolished the effects of Rab1A knockdown on cell 
      proliferation and apoptosis. In conclusion, Rab1A knockdown repressed 
      proliferation and promoted apoptosis in GC cells by inhibition of the mTOR/p70S6K 
      pathway.
CI  - Copyright (c) 2020 Elsevier Inc. All rights reserved.
FAU - Li, Zhong
AU  - Li Z
AD  - Department of General Surgery, Nanyang First People's Hospital, Nanyang, 473012, 
      China.
FAU - Li, Yuan
AU  - Li Y
AD  - Department of General Surgery, Nanyang First People's Hospital, Nanyang, 473012, 
      China.
FAU - Jia, Yunhao
AU  - Jia Y
AD  - Department of General Surgery, Nanyang First People's Hospital, Nanyang, 473012, 
      China.
FAU - Ding, Bo
AU  - Ding B
AD  - Department of General Surgery, Nanyang First People's Hospital, Nanyang, 473012, 
      China.
FAU - Yu, Jinsong
AU  - Yu J
AD  - Department of General Surgery, Nanyang First People's Hospital, Nanyang, 473012, 
      China. Electronic address: nsyyyjs@163.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200330
PL  - United States
TA  - Arch Biochem Biophys
JT  - Archives of biochemistry and biophysics
JID - 0372430
RN  - 0 (4,6-dimorpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine)
RN  - 0 (Morpholines)
RN  - 0 (RAB1A protein, human)
RN  - 0 (Triazines)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (Ribosomal Protein S6 Kinases, 70-kDa)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.6.5.2 (rab1 GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics/*physiology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics/*physiology
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Morpholines/pharmacology
MH  - Ribosomal Protein S6 Kinases, 70-kDa/metabolism
MH  - Signal Transduction/drug effects/genetics/*physiology
MH  - Stomach Neoplasms/*metabolism
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Triazines/pharmacology
MH  - Up-Regulation
MH  - rab1 GTP-Binding Proteins/genetics/*metabolism
OTO - NOTNLM
OT  - Apoptosis
OT  - Gastric cancer
OT  - Proliferation
OT  - Rab1A
OT  - mTOR/p70S6K pathway
COIS- Declaration of competing interest The authors declare that there are no conflicts 
      of interest.
EDAT- 2020/04/03 06:00
MHDA- 2020/07/14 06:00
CRDT- 2020/04/03 06:00
PHST- 2020/01/21 00:00 [received]
PHST- 2020/03/20 00:00 [revised]
PHST- 2020/03/27 00:00 [accepted]
PHST- 2020/04/03 06:00 [pubmed]
PHST- 2020/07/14 06:00 [medline]
PHST- 2020/04/03 06:00 [entrez]
AID - S0003-9861(20)30070-9 [pii]
AID - 10.1016/j.abb.2020.108352 [doi]
PST - ppublish
SO  - Arch Biochem Biophys. 2020 May 30;685:108352. doi: 10.1016/j.abb.2020.108352. 
      Epub 2020 Mar 30.