PMID- 36071871
OWN - NLM
STAT- MEDLINE
DCOM- 20220909
LR  - 20220916
IS  - 1942-0994 (Electronic)
IS  - 1942-0900 (Print)
IS  - 1942-0994 (Linking)
VI  - 2022
DP  - 2022
TI  - Dysregulation of EZH2/miR-138-5p Axis Contributes to Radiosensitivity in 
      Hepatocellular Carcinoma Cell by Downregulating Hypoxia-Inducible Factor 1 Alpha 
      (HIF-1alpha).
PG  - 7608712
LID - 10.1155/2022/7608712 [doi]
LID - 7608712
AB  - Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase involved in 
      cell proliferation, invasion, angiogenesis, and metastasis in various cancers, 
      including hepatocellular carcinoma (HCC). However, the role and molecular 
      mechanisms of EZH2 in HCC radiosensitivity remain unclear. Here, we show that 
      EZH2 is upregulated in HCC cells and the aberrantly overexpressed EZH2 is 
      associated with the poor prognosis of HCC patients. Using miRNA databases, we 
      identified miR-138-5p as a regulator of EZH2. We also found that miR-138-5p was 
      suppressed by EZH2-induced H3K27me3 in HCC cell lines. MiR-138-5p overexpression 
      and EZH2 knockdown enhanced cellular radiosensitivity while inhibiting cell 
      migration, invasion, and epithelial-mesenchymal transition (EMT). Analysis of 
      RNA-seq datasets revealed that the hypoxia-inducible factor-1 (HIF-1) signaling 
      pathway was the main enrichment pathway for differential genes after miR-138-5p 
      overexpression or EZH2 knockdown. Expression level of HIF-1alpha was significantly 
      suppressed after miR-138-5p overexpression or silencing of EZH2. HIF-1alpha silencing 
      mitigated resistance of HCC cells and inhibited EMT. This study establishes the 
      EZH2/miR-138-5p/HIF-1alpha as a potential therapeutic target for sensitizing HCC to 
      radiotherapy.
CI  - Copyright (c) 2022 Bing Bai et al.
FAU - Bai, Bing
AU  - Bai B
AUID- ORCID: 0000-0002-9584-8551
AD  - NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, 
      Changchun, Jilin 130021, China.
FAU - Liu, Ying
AU  - Liu Y
AUID- ORCID: 0000-0002-0012-2062
AD  - Department of Toxicology, School of Public Health, Jilin University, Changchun, 
      Jilin 130021, China.
FAU - Fu, Xue-Mei
AU  - Fu XM
AUID- ORCID: 0000-0003-4199-5393
AD  - Jilin Women and Children Health Hospital, Changchun, Jilin 130061, China.
FAU - Qin, Hai-Yan
AU  - Qin HY
AUID- ORCID: 0000-0001-5198-3359
AD  - Department of Plastic Surgery, China-Japan Union Hospital of Jilin University, 
      Changchun, Jilin 130031, China.
FAU - Li, Gao-Kai
AU  - Li GK
AUID- ORCID: 0000-0002-6335-8734
AD  - Department of Toxicology, School of Public Health, Jilin University, Changchun, 
      Jilin 130021, China.
FAU - Wang, Hai-Chen
AU  - Wang HC
AUID- ORCID: 0000-0002-6985-734X
AD  - NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, 
      Changchun, Jilin 130021, China.
FAU - Sun, Shi-Long
AU  - Sun SL
AUID- ORCID: 0000-0003-2911-9681
AD  - NHC Key Laboratory of Radiobiology, School of Public Health, Jilin University, 
      Changchun, Jilin 130021, China.
LA  - eng
PT  - Journal Article
DEP - 20220829
PL  - United States
TA  - Oxid Med Cell Longev
JT  - Oxidative medicine and cellular longevity
JID - 101479826
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (MIRN138 microRNA, human)
RN  - 0 (MicroRNAs)
RN  - EC 2.1.1.43 (EZH2 protein, human)
RN  - EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
SB  - IM
MH  - *Carcinoma, Hepatocellular/genetics/metabolism/radiotherapy
MH  - Cell Line, Tumor
MH  - *Enhancer of Zeste Homolog 2 Protein/genetics/metabolism
MH  - Humans
MH  - *Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
MH  - *Liver Neoplasms/genetics/metabolism/radiotherapy
MH  - *MicroRNAs/genetics/metabolism
MH  - Radiation Tolerance/genetics
PMC - PMC9444475
COIS- The authors declare no conflict of interest.
EDAT- 2022/09/09 06:00
MHDA- 2022/09/11 06:00
PMCR- 2022/08/29
CRDT- 2022/09/08 02:16
PHST- 2022/06/14 00:00 [received]
PHST- 2022/07/24 00:00 [revised]
PHST- 2022/08/03 00:00 [accepted]
PHST- 2022/09/08 02:16 [entrez]
PHST- 2022/09/09 06:00 [pubmed]
PHST- 2022/09/11 06:00 [medline]
PHST- 2022/08/29 00:00 [pmc-release]
AID - 10.1155/2022/7608712 [doi]
PST - epublish
SO  - Oxid Med Cell Longev. 2022 Aug 29;2022:7608712. doi: 10.1155/2022/7608712. 
      eCollection 2022.