PMID- 32554866
OWN - NLM
STAT- MEDLINE
DCOM- 20210308
LR  - 20210308
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 12
IP  - 12
DP  - 2020 Jun 18
TI  - Silencing of hsa_circ_0101145 reverses the epithelial-mesenchymal transition in 
      hepatocellular carcinoma via regulation of the miR-548c-3p/LAMC2 axis.
PG  - 11623-11635
LID - 10.18632/aging.103324 [doi]
AB  - Hepatocellular carcinoma (HCC) is a primary cause of cancer-related deaths 
      globally. While there have been advancements in HCC treatment and diagnosis, 
      incidence and mortality rates continue to rise. One study found that circular 
      RNAs functioned as competing endogenous RNAs, and constructed a gene-based 
      nomogram to estimate overall survival of HCC patients. Previous studies using 
      high-throughput sequencing suggested that hsa_circ_0101145 is abnormally 
      expressed in HCC, but the underlying mechanism is unknown. We performed RT-qPCR 
      to determine hsa_circ_0101145 and miR-548c-3p expression in HCC tissues. We used 
      fluorescence in situ hybridization (FISH) to detect hsa_circ_0101145 expression 
      and hsa_circ_0101145 subcellular localization in HCC tissues. hsa_circ_0101145 
      expression in HCC cells was selectively regulated. We determined LAMC2 and EMT 
      mRNA and protein levels by RT-qPCR and western blotting analysis, respectively. 
      We employed flow cytometry, and CCK8, Transwell, and wound healing assays to 
      monitor the cell cycle, cell proliferation, invasion, and migration, 
      respectively. We employed dual-luciferase reporter and RNA pulldown assays to 
      verify the relationship among hsa_circ_0101145, miR-548c-3p, and LAMC2. We 
      examined the effects of hsa_circ_0101145 on HCC cell metastasis and proliferation 
      in vivo using a subcutaneous xenograft model as well as intravenous tail 
      injection of nude mice. The data demonstrated that hsa_circ_0101145 was 
      significantly upregulated in both HCC tissues and cell lines. High 
      hsa_circ_0101145 expression was correlated with aggressive HCC phenotypes. 
      Downregulation of hsa_circ_0101145 suppressed HCC proliferation as well as 
      metastasis by targeting the miR-548c-3p/LAMC2 axis, which was examined using 
      luciferase reporter and RNA pulldown assays. Silencing of hsa_circ_0101145 
      suppressed the epithelial-mesenchymal transition in HCC. Downregulation of 
      miR-548c-3p or overexpression of LAMC2 restored migration and proliferation 
      abilities of HCC cells following hsa_circ_0101145 silencing. LAMC2 overexpression 
      reversed miR-548c-3p-induced cell migration and growth inhibition in vitro. In 
      summary, the findings illustrated that hsa_circ_0101145 silencing suppressed HCC 
      progression by functioning as an miR-548c-3p sponge to enhance LAMC2 expression. 
      Therefore, hsa_circ_0101145 could be an HCC treatment target.
FAU - Jin, Jinglan
AU  - Jin J
AD  - Department of Hepatology, The First Hospital of Jilin University, Changchun 
      130021, China.
FAU - Liu, Huan
AU  - Liu H
AD  - Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin 
      University, Changchun 130021, China.
FAU - Jin, Meishan
AU  - Jin M
AD  - Department of Pathology, The First Hospital of Jilin University, Changchun 
      130021, China.
FAU - Li, Wanyu
AU  - Li W
AD  - Department of Hepatology, The First Hospital of Jilin University, Changchun 
      130021, China.
FAU - Xu, Hongqin
AU  - Xu H
AD  - Department of Hepatology, The First Hospital of Jilin University, Changchun 
      130021, China.
FAU - Wei, Feng
AU  - Wei F
AD  - Department of Hepatobiliary and Pancreas Surgery, The First Hospital of Jilin 
      University, Changchun 130021, China.
LA  - eng
PT  - Journal Article
PT  - Observational Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20200618
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (LAMC2 protein, human)
RN  - 0 (Laminin)
RN  - 0 (MIRN548 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Circular)
SB  - IM
MH  - Animals
MH  - Carcinoma, Hepatocellular/*genetics/mortality/secondary
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Epithelial-Mesenchymal Transition/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic
MH  - Gene Silencing
MH  - Humans
MH  - Kaplan-Meier Estimate
MH  - Laminin/*genetics
MH  - Liver/pathology
MH  - Liver Neoplasms/*genetics/mortality/pathology
MH  - Male
MH  - Mice
MH  - MicroRNAs/*metabolism
MH  - Middle Aged
MH  - RNA, Circular/genetics/*metabolism
MH  - Xenograft Model Antitumor Assays
PMC - PMC7343517
OTO - NOTNLM
OT  - LAMC2
OT  - epithelial-mesenchymal transition
OT  - hepatocellular
OT  - hsa_circ_0101145
OT  - miR-548c-3p
COIS- CONFLICTS OF INTEREST: The authors declare that there are no conflicts of 
      interest.
EDAT- 2020/06/20 06:00
MHDA- 2021/03/09 06:00
PMCR- 2020/06/30
CRDT- 2020/06/20 06:00
PHST- 2020/03/06 00:00 [received]
PHST- 2020/04/28 00:00 [accepted]
PHST- 2020/06/20 06:00 [pubmed]
PHST- 2021/03/09 06:00 [medline]
PHST- 2020/06/20 06:00 [entrez]
PHST- 2020/06/30 00:00 [pmc-release]
AID - 103324 [pii]
AID - 10.18632/aging.103324 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2020 Jun 18;12(12):11623-11635. doi: 10.18632/aging.103324. 
      Epub 2020 Jun 18.