PMID- 33858418
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210418
IS  - 1475-2867 (Print)
IS  - 1475-2867 (Electronic)
IS  - 1475-2867 (Linking)
VI  - 21
IP  - 1
DP  - 2021 Apr 15
TI  - Circular RNA hsa_circ_0003288 induces EMT and invasion by regulating 
      hsa_circ_0003288/miR-145/PD-L1 axis in hepatocellular carcinoma.
PG  - 212
LID - 10.1186/s12935-021-01902-2 [doi]
LID - 212
AB  - BACKGROUND: Epithelial-mesenchymal transition (EMT) has been associated with 
      wound healing, tumorigenesis, and metastasis. Circular RNAs (circRNAs) are 
      functional non-coding RNAs involved in multiple human cancers. However, whether 
      and how circRNAs contribute to the EMT in hepatocellular carcinomas (HCC) remains 
      to be deciphered. In this study, we investigated the regulation and function of 
      hsa_circ_0003288 on programmed death-1 ligand 1 (PD-L1) during EMT and HCC 
      invasiveness. METHODS: Hsa_circ_0003288 expression was measured by real-time 
      quantitative reverse transcriptase PCR (qRT-PCR). Luciferase reporter assays, RNA 
      pull-down assay and fluorescence in situ hybridization (FISH) were used to 
      determine the correlation between hsa_circ_0003288 and miR-145 and between 
      miR-145 and PD-L1. Furthermore, ectopic overexpression and siRNA-mediated 
      downregulation of hsa_circ_0003288, transwell assays, and in vivo studies were 
      used to determine the function of hsa_circ_0003288 on the EMT and invasiveness of 
      L02 and HCC cells. RESULTS: miR-145 directly targeted the PD-L1 3'-untranslated 
      region (UTR) region, and hsa_circ_0003288 acted as a miR-145 sponge to regulate 
      PD-L1 expression. Overexpression of hsa_circ_0003288 increased PD-L1 levels and 
      promoted EMT, migration, and invasiveness of L02 cells. These observations were 
      reversed after knockdown of hsa_circ_0003288 in HepG2 and Huh7 cells. 
      Overexpression of PD-L1 rescued EMT, migration, and invasiveness of HepG2 and 
      Huh7 cells after knockdown of hsa_circ_0003288. Furthermore, hsa_circ_0003288 
      knockdown reduced EMT in in vivo studies. Hsa_circ_0003288/PD-L1 axis was found 
      to mediate the metastatic phenotypes via the PI3K/Akt pathway in HCC. 
      Additionally, expression levels of hsa_circ_0003288 were increased and positively 
      correlated with PD-L1 expression in HCC tissues. CONCLUSION: Our findings 
      demonstrated that hsa_circ_0003288 promoted EMT and invasion of HCC via the 
      hsa_circ_0003288/miR-145/PD-L1 axis through the PI3K/Akt pathway. Targeting 
      hsa_circ_0003288 may be a therapeutic strategy for the treatment of HCC.
FAU - Xu, Guili
AU  - Xu G
AUID- ORCID: 0000-0003-1183-0627
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China.
FAU - Zhang, Peng
AU  - Zhang P
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China.
FAU - Liang, Hansi
AU  - Liang H
AD  - Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of 
      Soochow University, Suzhou, Jiangsu, 215006, China.
FAU - Xu, Yunhua
AU  - Xu Y
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China.
FAU - Shen, Jian
AU  - Shen J
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China.
FAU - Wang, Wansheng
AU  - Wang W
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China.
FAU - Li, Mingming
AU  - Li M
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China.
FAU - Huang, Jintao
AU  - Huang J
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China.
FAU - Ni, Caifang
AU  - Ni C
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China. szncf@suda.edu.cn.
FAU - Zhang, Xueguang
AU  - Zhang X
AD  - Jiangsu Institute of Clinical Immunology, The First Affiliated Hospital of 
      Soochow University, Suzhou, Jiangsu, 215006, China. xueguangzh@126.com.
FAU - Zhu, Xiaoli
AU  - Zhu X
AD  - Department of Interventional Radiology, First Affiliated Hospital of Soochow 
      University, 188 Shizi Street, Suzhou, Jiangsu, 215006, China. 
      zhuxiaoli@suda.edu.cn.
LA  - eng
GR  - 81771945/Natural Science Foundation of China/
PT  - Journal Article
DEP - 20210415
PL  - England
TA  - Cancer Cell Int
JT  - Cancer cell international
JID - 101139795
PMC - PMC8048300
OTO - NOTNLM
OT  - 0,003,288
OT  - Circ
OT  - EMT
OT  - Hepatocellular carcinoma
OT  - Hsa
OT  - MiR-145
OT  - PD-L1
COIS- The authors declare that they have no competing interests.
EDAT- 2021/04/17 06:00
MHDA- 2021/04/17 06:01
PMCR- 2021/04/15
CRDT- 2021/04/16 05:36
PHST- 2020/09/24 00:00 [received]
PHST- 2021/03/30 00:00 [accepted]
PHST- 2021/04/16 05:36 [entrez]
PHST- 2021/04/17 06:00 [pubmed]
PHST- 2021/04/17 06:01 [medline]
PHST- 2021/04/15 00:00 [pmc-release]
AID - 10.1186/s12935-021-01902-2 [pii]
AID - 1902 [pii]
AID - 10.1186/s12935-021-01902-2 [doi]
PST - epublish
SO  - Cancer Cell Int. 2021 Apr 15;21(1):212. doi: 10.1186/s12935-021-01902-2.