PMID- 35170199
OWN - NLM
STAT- MEDLINE
DCOM- 20220412
LR  - 20220531
IS  - 1582-4934 (Electronic)
IS  - 1582-1838 (Print)
IS  - 1582-1838 (Linking)
VI  - 26
IP  - 8
DP  - 2022 Apr
TI  - Hsa_circ_0003945 promotes progression of hepatocellular carcinoma by mediating 
      miR-34c-5p/LGR4/beta-catenin axis activity.
PG  - 2218-2229
LID - 10.1111/jcmm.17243 [doi]
AB  - Accumulating evidence suggests that circular RNAs (circRNAs) play essential roles 
      in regulating cancer progression, but many circRNAs in hepatocellular carcinoma 
      (HCC) remain unknown. Dysregulated circRNAs in HCC were identified through 
      bioinformatics analysis of Gene Expression Omnibus data sets. Quantitative 
      real-time PCR (qRT-PCR), Sanger sequencing, RNase R digestion and actinomycin D 
      treatment were conducted to confirm the characterization of circRNAs. CCK-8, 
      wound-healing and Transwell assays were performed to assess the functional roles 
      of Hsa_circ_0003945 (Circ_0003945) in HCC cell lines. Subcellular fractionation 
      and fluorescence in situ hybridization (FISH) were performed to locate 
      Circ_0003945 in HCC cells. Dual-luciferase reporter assay was executed to verify 
      the binding of Circ_0003945 to microRNAs (miRNAs) or the miRNAs to their target 
      genes. In this study, we found that Circ_0003945 was upregulated in HCC tissue, 
      and higher Circ_0003945 expression was positively correlated with tumour size and 
      tumour stage. Furthermore, high plasma levels of circulating Circ_0003945 were 
      confirmed in HCC patients compared with those in non-HCC groups. The functional 
      experiments revealed that overexpression or knockdown of Circ_0003945 promoted or 
      attenuated tumour growth and migration, respectively. Mechanistically, 
      Circ_0003945 might exert as a miR-34c-5p sponge to upregulate the expression of 
      leucine-rich repeat-containing G protein-coupled receptor 4 (LGR4), activating 
      the beta-catenin pathway, and finally facilitating HCC progression. Additionally, a 
      beta-catenin activator could reverse the effect of Circ_0003945 knockdown. In 
      conclusion, Circ_0003945 exerts a tumour-promoting role in HCC cells by 
      regulating the miR-34c-5p/LGR4/beta-catenin axis, which may be a potential target 
      for HCC therapy.
CI  - (c) 2022 The Authors. Journal of Cellular and Molecular Medicine published by 
      Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
FAU - Lyu, Li-Hua
AU  - Lyu LH
AD  - Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, 
      Shanghai, China.
FAU - Zhang, Chun-Yan
AU  - Zhang CY
AD  - Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, 
      Shanghai, China.
AD  - Department of Laboratory Medicine, Xiamen Branch, Zhongshan Hospital, Fudan 
      University, Xiamen, China.
FAU - Yang, Wen-Jing
AU  - Yang WJ
AD  - Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, 
      Shanghai, China.
FAU - Jin, An-Li
AU  - Jin AL
AD  - Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, 
      Shanghai, China.
FAU - Zhu, Jie
AU  - Zhu J
AD  - Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, 
      Shanghai, China.
FAU - Wang, Hao
AU  - Wang H
AD  - Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, 
      Shanghai, China.
FAU - Liu, Te
AU  - Liu T
AUID- ORCID: 0000-0003-3976-3489
AD  - Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of 
      Traditional Chinese Medicine, Shanghai, China.
FAU - Wang, Bei-Li
AU  - Wang BL
AD  - Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, 
      Shanghai, China.
AD  - Cancer center, Zhong Shan Hospital, Fudan University, Shanghai, China.
FAU - Cheng, Jian-Wen
AU  - Cheng JW
AD  - Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan 
      Hospital, Fudan University, Shanghai, China.
AD  - Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 
      Shanghai, China.
FAU - Yang, Xin-Rong
AU  - Yang XR
AD  - Department of Liver Surgery & Transplantation, Liver Cancer Institute, Zhongshan 
      Hospital, Fudan University, Shanghai, China.
AD  - Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, 
      Shanghai, China.
FAU - Guo, Wei
AU  - Guo W
AUID- ORCID: 0000-0003-4406-1094
AD  - Department of Laboratory Medicine, Zhongshan Hospital, Fudan University, 
      Shanghai, China.
AD  - Department of Laboratory Medicine, Xiamen Branch, Zhongshan Hospital, Fudan 
      University, Xiamen, China.
AD  - Cancer center, Zhong Shan Hospital, Fudan University, Shanghai, China.
AD  - Department of Laboratory Medicine, Wusong Branch, Zhongshan Hospital, Fudan 
      University, Shanghai, China.
LA  - eng
GR  - 2018ZSLC05/Shanghai Municipal Key Clinical Specialty, and specialized fund for 
      the clinical researches of Zhongshan Hospital affiliated Fudan University/
GR  - 81772551/National Natural Science Foundation of China/
GR  - 81972000/National Natural Science Foundation of China/
GR  - 81902139/National Natural Science Foundation of China/
GR  - 81772578/National Natural Science Foundation of China/
GR  - 81872355/National Natural Science Foundation of China/
GR  - 82072715/National Natural Science Foundation of China/
GR  - 19441905000/Shanghai "Rising Stars of Medical Talent" Youth Development Program 
      (Outstanding Youth Medical Talents), the Projects from the Shanghai Science and 
      Technology Commission/
GR  - YDZX20193502000002/key medical and health projects of Xiamen/
GR  - 2019YFC1315800/National Key R&D Program of China/
GR  - 2019YFC1315802/National Key R&D Program of China/
GR  - 81830102/State Key Program of National Natural Science of China/
GR  - 2019CXJQ02/Shanghai Municipal Health Commission Collaborative Innovation Cluster 
      Project/
PT  - Journal Article
DEP - 20220216
PL  - England
TA  - J Cell Mol Med
JT  - Journal of cellular and molecular medicine
JID - 101083777
RN  - 0 (CTNNB1 protein, human)
RN  - 0 (LGR4 protein, human)
RN  - 0 (MIRN34 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
RN  - 0 (Receptors, G-Protein-Coupled)
RN  - 0 (beta Catenin)
SB  - IM
MH  - *Carcinoma, Hepatocellular/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Humans
MH  - In Situ Hybridization, Fluorescence
MH  - *Liver Neoplasms/pathology
MH  - *MicroRNAs/genetics/metabolism
MH  - RNA, Circular/genetics
MH  - *Receptors, G-Protein-Coupled/metabolism
MH  - Signal Transduction
MH  - *beta Catenin/genetics/metabolism
PMC - PMC8995453
OTO - NOTNLM
OT  - Circ_0003945
OT  - hepatocellular carcinoma
OT  - leucine-rich repeat-containing G protein-coupled receptor 4
OT  - miR-34c-5p
OT  - tumour progression
COIS- The authors declare no competing interests.
EDAT- 2022/02/17 06:00
MHDA- 2022/04/13 06:00
PMCR- 2022/04/01
CRDT- 2022/02/16 05:53
PHST- 2022/01/24 00:00 [revised]
PHST- 2021/09/22 00:00 [received]
PHST- 2022/01/31 00:00 [accepted]
PHST- 2022/02/17 06:00 [pubmed]
PHST- 2022/04/13 06:00 [medline]
PHST- 2022/02/16 05:53 [entrez]
PHST- 2022/04/01 00:00 [pmc-release]
AID - JCMM17243 [pii]
AID - 10.1111/jcmm.17243 [doi]
PST - ppublish
SO  - J Cell Mol Med. 2022 Apr;26(8):2218-2229. doi: 10.1111/jcmm.17243. Epub 2022 Feb 
      16.