PMID- 34487732
OWN - NLM
STAT- MEDLINE
DCOM- 20211206
LR  - 20211214
IS  - 1090-2422 (Electronic)
IS  - 0014-4827 (Linking)
VI  - 408
IP  - 2
DP  - 2021 Nov 15
TI  - ESR1 mediated circ_0004018 suppresses angiogenesis in hepatocellular carcinoma 
      via recruiting FUS and stabilizing TIMP2 expression.
PG  - 112804
LID - S0014-4827(21)00357-8 [pii]
LID - 10.1016/j.yexcr.2021.112804 [doi]
AB  - Angiogenesis has been certified to account for tumor pathobiology. Circular RNAs 
      (circRNAs) have been demonstrated to be involved in angiogenesis-related 
      diseases, including hepatocellular carcinoma (HCC). Nevertheless, the regulatory 
      roles of most circRNAs remain obscure. This study aims to uncover the function of 
      hsa_circ_0004018 on angiogenesis in HCC. Firstly, quantitative real-time RT-PCR 
      (RT-qPCR) analyzed that circ_0004018 was definitely down-regulated in HCC. 
      Western blot analysis was conducted to detect the protein level of fused protein 
      in sarcoma (FUS) and TIMP metallopeptidase inhibitor 2 (TIMP2). Functional assays 
      were carried out to assess the impacts of circ_0004018 on HCC. From the 
      experimental results, we found that overexpression of circ_0004018 significantly 
      inhibited angiogenesis in HCC. The regulatory mechanism of circ_0004018 in HCC 
      was determined by chromatin immunoprecipitation (ChIP), luciferase reporter 
      assays and RNA immunoprecipitation (RIP) assay. Therefore, we proved that 
      estrogen receptor 1 (ESR1) mediated circ_0004018 regulated TIMP2 by recruiting 
      FUS. A series of rescue assays verified that circ_0004018 participated in 
      angiogenesis in HCC via modulating TIMP2. In summary, this paper disclosed that 
      ESR1 activated circ_0004018 inhibited angiogenesis in HCC via binding to FUS and 
      stabilizing TIMP2 expression.
CI  - Copyright (c) 2021 Elsevier Inc. All rights reserved.
FAU - Wu, Yanli
AU  - Wu Y
AD  - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hankou, Wuhan, 430030, Hubei, PR China.
FAU - Zhang, Mingsheng
AU  - Zhang M
AD  - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hankou, Wuhan, 430030, Hubei, PR China.
FAU - Bi, Xiaojun
AU  - Bi X
AD  - Department of Ultrasound, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hankou, Wuhan, 430030, Hubei, PR China.
FAU - Hao, Li
AU  - Hao L
AD  - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hankou, Wuhan, 430030, Hubei, PR China.
FAU - Liu, Rong
AU  - Liu R
AD  - Department of Stomatology, Union Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hankou, Wuhan, 430022, Hubei, PR China.
FAU - Zhang, Haiyan
AU  - Zhang H
AD  - Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong 
      University of Science and Technology, Hankou, Wuhan, 430030, Hubei, PR China. 
      Electronic address: zhangchefu1@163.com.
LA  - eng
PT  - Journal Article
DEP - 20210903
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (ESR1 protein, human)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (FUS protein, human)
RN  - 0 (RNA, Circular)
RN  - 0 (RNA-Binding Protein FUS)
RN  - 0 (TIMP2 protein, human)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
SB  - IM
MH  - Animals
MH  - Apoptosis/genetics
MH  - Carcinoma, Hepatocellular/*genetics/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Estrogen Receptor alpha/*genetics
MH  - Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Liver Neoplasms/genetics/pathology
MH  - Mice
MH  - Neovascularization, Pathologic/*genetics/pathology
MH  - RNA, Circular/*genetics
MH  - RNA-Binding Protein FUS/*genetics
MH  - Tissue Inhibitor of Metalloproteinase-2/*genetics
MH  - Xenograft Model Antitumor Assays
OTO - NOTNLM
OT  - Angiogenesis
OT  - FUS
OT  - Hepatocellular carcinoma
OT  - TIMP2
OT  - hsa_circ_0004018
EDAT- 2021/09/07 06:00
MHDA- 2021/12/15 06:00
CRDT- 2021/09/06 20:10
PHST- 2020/08/24 00:00 [received]
PHST- 2021/08/22 00:00 [revised]
PHST- 2021/08/25 00:00 [accepted]
PHST- 2021/09/07 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/09/06 20:10 [entrez]
AID - S0014-4827(21)00357-8 [pii]
AID - 10.1016/j.yexcr.2021.112804 [doi]
PST - ppublish
SO  - Exp Cell Res. 2021 Nov 15;408(2):112804. doi: 10.1016/j.yexcr.2021.112804. Epub 
      2021 Sep 3.