PMID- 36217445
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221012
IS  - 2253-5969 (Print)
IS  - 2253-5969 (Electronic)
IS  - 2253-5969 (Linking)
VI  - 9
DP  - 2022
TI  - Circular RNA circRASSF5 Functions as an Anti-Oncogenic Factor in Hepatocellular 
      Carcinoma by Acting as a Competitive Endogenous RNA Through Sponging miR-331-3p.
PG  - 1041-1056
LID - 10.2147/JHC.S376063 [doi]
AB  - OBJECTIVE: Recently, emerging studies have validated that circular RNAs 
      participate in multiple biological progresses in various human malignant tumors, 
      including hepatocellular carcinoma (HCC). However, until now, the elucidated 
      mechanism of circular RNAs is only the tip of the iceberg. In this study, we 
      firstly identify a novel circular RNA circRASSF5 (the only circular RNA derived 
      from the RASSF5 gene), and attempt to investigate its biological function and 
      underlying mechanism in HCC. METHODS: qRT-PCR, Western blotting and IHC were 
      applied to detect the expression of related genes. CCK-8 assay, EdU staining, 
      wound healing and transwell assays were used to investigate HCC proliferation, 
      migration and invasion abilities. Animal model studies were included to 
      investigate the function of circRASSF5 in HCC tumorigenesis and metastasis. RNA 
      pull-down assay, luciferase reporter assay and FISH (fluorescence in situ 
      hybridization) assay were performed to explore the potential biological mechanism 
      underlying circRASSF5 function in HCC. RESULTS: CircRASSF5 is obviously 
      downregulated in both HCC tissues and cell lines. Low level of circRASSF5 is 
      negatively associated with larger tumor size, severe vascular invasion, more 
      portal vein tumor embolus and unfavorable prognosis. Loss-of-function assay 
      reveals that circRASSF5 remarkably impedes the growth and metastasis of HCC cells 
      in vitro and in vivo. Mechanistically, circRASSF5 directly interacts with 
      miR-331-3p as a sponge, and then enhances the expression of PH domain and 
      leucine-rich repeat protein phosphatase (PHLPP), thus restraining the progression 
      of HCC cells. CONCLUSION: Altogether, we validate that circRASSF5 is a tumor 
      suppressor in HCC, which competitively sponges with miR-331-3p and then enhances 
      the tumor inhibitory effect of PHLPP, indicating the potential application value 
      of circRASSF5 for HCC diagnosis and clinical treatment.
CI  - (c) 2022 Zhou et al.
FAU - Zhou, Zhao
AU  - Zhou Z
AUID- ORCID: 0000-0001-7015-6076
AD  - Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical 
      College of Nanjing Medical University, Nanjing, People's Republic of China.
AD  - The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, 
      Changzhou, People's Republic of China.
FAU - Cui, Xiaohan
AU  - Cui X
AD  - Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical 
      College of Nanjing Medical University, Nanjing, People's Republic of China.
AD  - The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, 
      Changzhou, People's Republic of China.
FAU - Gao, Peng
AU  - Gao P
AD  - The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, 
      Changzhou, People's Republic of China.
FAU - Zhang, Xudong
AU  - Zhang X
AD  - The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, 
      Changzhou, People's Republic of China.
FAU - Zhu, Chunfu
AU  - Zhu C
AD  - The Affiliated Changzhou NO.2 People's Hospital of Nanjing Medical University, 
      Changzhou, People's Republic of China.
FAU - Sun, Beicheng
AU  - Sun B
AD  - Department of Hepatobiliary Surgery of Nanjing Drum Tower Hospital, Clinical 
      College of Nanjing Medical University, Nanjing, People's Republic of China.
LA  - eng
PT  - Journal Article
DEP - 20221004
PL  - New Zealand
TA  - J Hepatocell Carcinoma
JT  - Journal of hepatocellular carcinoma
JID - 101674775
PMC - PMC9547604
OTO - NOTNLM
OT  - HCC
OT  - PHLPP
OT  - circRASSF5
OT  - miR-331-3p
COIS- The authors report no conflicts of interest in this work.
EDAT- 2022/10/12 06:00
MHDA- 2022/10/12 06:01
PMCR- 2022/10/04
CRDT- 2022/10/11 01:48
PHST- 2022/06/05 00:00 [received]
PHST- 2022/09/19 00:00 [accepted]
PHST- 2022/10/11 01:48 [entrez]
PHST- 2022/10/12 06:00 [pubmed]
PHST- 2022/10/12 06:01 [medline]
PHST- 2022/10/04 00:00 [pmc-release]
AID - 376063 [pii]
AID - 10.2147/JHC.S376063 [doi]
PST - epublish
SO  - J Hepatocell Carcinoma. 2022 Oct 4;9:1041-1056. doi: 10.2147/JHC.S376063. 
      eCollection 2022.