PMID- 33153478
OWN - NLM
STAT- MEDLINE
DCOM- 20210803
LR  - 20210803
IS  - 1476-4598 (Electronic)
IS  - 1476-4598 (Linking)
VI  - 19
IP  - 1
DP  - 2020 Nov 5
TI  - circCUL2 regulates gastric cancer malignant transformation and cisplatin 
      resistance by modulating autophagy activation via miR-142-3p/ROCK2.
PG  - 156
LID - 10.1186/s12943-020-01270-x [doi]
LID - 156
AB  - BACKGROUND: Circular RNAs (circRNAs) are a class of noncoding RNAs (ncRNAs) and 
      can modulate gene expression by binding to miRNAs; further, circRNAs have been 
      shown to participate in several pathological processes. However, the expression 
      and biological function of circCUL2 in gastric cancer (GC) remains largely 
      unknown. METHODS: circRNA microarrays and quantitative real-time PCR (qRT-PCR) 
      were used to identify differentially expressed circRNAs in GC tissues and cell 
      lines. circCUL2 knockdown and overexpression were performed to indicate the 
      functional role of circCUL2 in vitro and in vivo. The expression and regulation 
      of circCUL2, miR-142-3p and ROCK2 were evaluated using fluorescence in situ 
      hybridization (FISH), dual-luciferase assays, RNA pull-down assays, RNA 
      immunoprecipitation (RIP) and rescue experiments. Furthermore, the regulation of 
      cisplatin sensitivity and autophagy by circCUL2/miR-142-3p/ROCK2 was demonstrated 
      by cellular apoptosis assays, western blot, immunofluorescence and transmission 
      electron microscopy analyses. RESULTS: The level of circCUL2, which is stable and 
      cytoplasmically localized, was significantly reduced in GC tissues and cells. 
      Overexpressed circCUL2 inhibited malignant transformation in vitro and 
      tumorigenicity in vivo. In the AGS and SGC-7901 cell lines, circCUL2 sponged 
      miR-142-3p to regulate ROCK2, thus modulating tumor progression. Furthermore, in 
      the AGS/DDP and SGC-7901/DDP cell lines, circCUL2 regulated cisplatin sensitivity 
      through miR-142-3p/ROCK2-mediated autophagy activation. CONCLUSION: circCUL2 may 
      function as a tumor suppressor and regulator of cisplatin sensitivity through 
      miR-142-3p/ROCK2-mediated autophagy activation, which could be a key mechanism 
      and therapeutic target for GC.
FAU - Peng, Lei
AU  - Peng L
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Sang, Huaiming
AU  - Sang H
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Wei, Shuchun
AU  - Wei S
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
AD  - Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 
      China.
FAU - Li, Yuanyuan
AU  - Li Y
AD  - Department of endocrinology, Children's Hospital of Nanjing Medical University, 
      Nanjing, China.
FAU - Jin, Duochen
AU  - Jin D
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Zhu, Xudong
AU  - Zhu X
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Li, Xuan
AU  - Li X
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Dang, Yini
AU  - Dang Y
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China.
FAU - Zhang, Guoxin
AU  - Zhang G
AD  - Department of Gastroenterology, First Affiliated Hospital of Nanjing Medical 
      University, Nanjing, China. guoxinz@njmu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20201105
PL  - England
TA  - Mol Cancer
JT  - Molecular cancer
JID - 101147698
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (CUL2 protein, human)
RN  - 0 (Cullin Proteins)
RN  - 0 (MIRN142 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - EC 2.7.11.1 (ROCK2 protein, human)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - Q20Q21Q62J (Cisplatin)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents
MH  - Apoptosis
MH  - *Autophagy
MH  - Biomarkers, Tumor/genetics/metabolism
MH  - Cell Movement
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic/drug effects/genetics/pathology
MH  - Cisplatin/*pharmacology
MH  - Cullin Proteins/genetics
MH  - *Drug Resistance, Neoplasm
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - MicroRNAs/*genetics
MH  - Middle Aged
MH  - Prognosis
MH  - RNA, Circular/*genetics
MH  - Stomach Neoplasms/drug therapy/genetics/*pathology/surgery
MH  - Survival Rate
MH  - Tumor Cells, Cultured
MH  - Xenograft Model Antitumor Assays
MH  - rho-Associated Kinases/genetics/*metabolism
PMC - PMC7643398
OTO - NOTNLM
OT  - Autophagy
OT  - Cisplatin resistance
OT  - Gastric cancer
OT  - ROCK2
OT  - circCUL2
OT  - miR-142-3p
COIS- The authors declare that they have no conflicts of interest.
EDAT- 2020/11/07 06:00
MHDA- 2021/08/04 06:00
PMCR- 2020/11/05
CRDT- 2020/11/06 05:36
PHST- 2020/05/05 00:00 [received]
PHST- 2020/10/16 00:00 [accepted]
PHST- 2020/11/06 05:36 [entrez]
PHST- 2020/11/07 06:00 [pubmed]
PHST- 2021/08/04 06:00 [medline]
PHST- 2020/11/05 00:00 [pmc-release]
AID - 10.1186/s12943-020-01270-x [pii]
AID - 1270 [pii]
AID - 10.1186/s12943-020-01270-x [doi]
PST - epublish
SO  - Mol Cancer. 2020 Nov 5;19(1):156. doi: 10.1186/s12943-020-01270-x.