PMID- 34638280
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20211016
IS  - 2072-6694 (Print)
IS  - 2072-6694 (Electronic)
IS  - 2072-6694 (Linking)
VI  - 13
IP  - 19
DP  - 2021 Sep 24
TI  - Epigenetic Silencing of miR-33b Promotes Peritoneal Metastases of Ovarian Cancer 
      by Modulating the TAK1/FASN/CPT1A/NF-kappaB Axis.
LID - 10.3390/cancers13194795 [doi]
LID - 4795
AB  - Peritoneal metastases are frequently found in high-grade serous carcinoma (HGSOC) 
      patients and are commonly associated with a poor prognosis. The tumor 
      microenvironment (TME) is a complex milieu that plays a critical role in 
      epigenetic alterations driving tumor development and metastatic progression. 
      However, the impact of epigenetic alterations on metastatic ovarian cancer cells 
      in the harsh peritoneal microenvironment remains incompletely understood. Here, 
      we identified that miR-33b is frequently silenced by promoter hypermethylation in 
      HGSOC cells derived from metastatic omental tumor tissues. Enforced expression of 
      miR-33b abrogates the oncogenic properties of ovarian cancer cells cocultured in 
      omental conditioned medium (OCM), which mimics the ascites microenvironment, and 
      in vivo tumor growth. Of note, restoration of miR-33b inhibited OCM-upregulated 
      de novo lipogenesis and fatty acid beta-oxidation in ovarian cancer cells, 
      indicating that miR-33b may play a novel tumor suppressor role in the 
      lipid-mediated oncogenic properties of metastatic ovarian cancer cells found in 
      the omentum. Mechanistic studies demonstrated that miR-33b directly targets 
      transforming growth factor beta-activated kinase 1 (TAK1), thereby suppressing 
      the activities of fatty acid synthase (FASN) and carnitine palmitoyltransferase 
      1A (CPT1A) in modulating lipid metabolic activities and simultaneously inhibiting 
      the phosphorylation of NF-kappaB signaling to govern the oncogenic behaviors of 
      ovarian cancer cells. Thus, our data suggest that a lipid-rich microenvironment 
      may cause epigenetic silencing of miR-33b, which negatively modulates ovarian 
      cancer peritoneal metastases, at least in part, by suppressing 
      TAK1/FASN/CPT1A/NF-kappaB signaling.
FAU - Wang, Xueyu
AU  - Wang X
AD  - Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Hong Kong, China.
FAU - Yung, Mingo M H
AU  - Yung MMH
AUID- ORCID: 0000-0003-0903-1164
AD  - Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Hong Kong, China.
FAU - Sharma, Rakesh
AU  - Sharma R
AD  - Centre for PanorOmic Sciences Proteomics and Metabolomics Core, Li Ka Shing 
      Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
FAU - Chen, Fushun
AU  - Chen F
AD  - Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Hong Kong, China.
FAU - Poon, Ying-Tung
AU  - Poon YT
AD  - Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Hong Kong, China.
FAU - Lam, Wai-Yip
AU  - Lam WY
AD  - Lee's Pharmaceutical (HK) Ltd., 1/F Building 20E, Phase 3, Hong Kong Science 
      Park, Shatin, Hong Kong, China.
FAU - Li, Benjamin
AU  - Li B
AD  - Lee's Pharmaceutical (HK) Ltd., 1/F Building 20E, Phase 3, Hong Kong Science 
      Park, Shatin, Hong Kong, China.
FAU - Ngan, Hextan Y S
AU  - Ngan HYS
AD  - Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Hong Kong, China.
FAU - Chan, Karen K L
AU  - Chan KKL
AD  - Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Hong Kong, China.
FAU - Chan, David W
AU  - Chan DW
AUID- ORCID: 0000-0002-6951-3467
AD  - Department of Obstetrics & Gynaecology, Li Ka Shing Faculty of Medicine, The 
      University of Hong Kong, Hong Kong, China.
LA  - eng
GR  - UIM367/University-Industry Collaboration Programme, the Innovation and Technology 
      Commission, (Hong Kong)/
PT  - Journal Article
DEP - 20210924
PL  - Switzerland
TA  - Cancers (Basel)
JT  - Cancers
JID - 101526829
PMC - PMC8508465
OTO - NOTNLM
OT  - DNA methylation
OT  - lipid metabolism
OT  - miR-33b
OT  - omental metastases
OT  - ovarian cancer
COIS- The authors declare no conflict interests.
EDAT- 2021/10/14 06:00
MHDA- 2021/10/14 06:01
PMCR- 2021/09/24
CRDT- 2021/10/13 01:01
PHST- 2021/08/19 00:00 [received]
PHST- 2021/09/10 00:00 [revised]
PHST- 2021/09/20 00:00 [accepted]
PHST- 2021/10/13 01:01 [entrez]
PHST- 2021/10/14 06:00 [pubmed]
PHST- 2021/10/14 06:01 [medline]
PHST- 2021/09/24 00:00 [pmc-release]
AID - cancers13194795 [pii]
AID - cancers-13-04795 [pii]
AID - 10.3390/cancers13194795 [doi]
PST - epublish
SO  - Cancers (Basel). 2021 Sep 24;13(19):4795. doi: 10.3390/cancers13194795.