Epstein–Barr Virus‐Encoded MicroRNA‐BART18‐3p Promotes Colorectal Cancer Progression by Targeting De Novo Lipogenesis. Issue 35 (28th October 2022)

• Record Type: Journal Article
• Authors: Meng, Qingtao; Sun, Hao; Wu, Shenshen; Familiari, Giuseppe; Relucenti, Michela; Aschner, Michael; Li, Xiaobo; Chen, Rui
• Is Part Of: Advanced science. Volume 9:Issue 35(2022)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-10-28
• Subjects: colorectal cancer (CRC) -- de novo lipogenesis -- Epstein–Barr virus (EBV) -- lactate dehydrogenase A (LDHA) -- microRNA; Science -- Periodicals; 505
• DOI: 10.1002/advs.202202116
• Languages: English
• ISSNs: 2198-3844

Abstract

Abstract: The Epstein–Barr virus (EBV) genome encodes a cluster of 22 viral microRNAs, called miR‐BamHI‐A rightward transcripts (miR‐BARTs), which are shown to promote the development of cancer. Here, this study reports that EBV‐miR‐BART18‐3p is highly expressed in colorectal cancer (CRC) and is closely associated with the pathological and advanced clinical stages of CRC. Ectopic expression of EBV‐miR‐BART18‐3p leads to increased migration and invasion capacities of CRC cells in vitro and causes tumor metastasis in vivo. Mechanistically, EBV‐miR‐BART18‐3p activates the hypoxia inducible factor 1 subunit alpha/lactate dehydrogenase A axis by targeting Sirtuin, which promotes lactate accumulation and acetyl‐CoA production in CRC cells under hypoxic condition. Increased acetyl‐CoA utilization subsequently leads to histone acetylation of fatty acid synthase and fatty acid synthase‐dependent fat synthesis, which in turn drives de novo lipogenesis. The oncogenic role of EBV‐miR‐BART18‐3p is confirmed in the patient‐derived tumor xenograft mouse model. Altogether, the findings define a novel mechanism of EBV‐miR‐BART18‐3p in CRC development through the lipogenesis pathway and provide a potential clinical intervention target for CRC. Abstract : EBV‐miR‐BART18‐3p is highly expressed in colorectal cancer (CRC) and is closely associated with the pathological and advanced clinical stages of CRC. EBV‐miR‐BART18‐3p promotes histone acetylation and enhances de novo lipogenesis by upregulating lactate dehydrogenase A‐mediated metabolic processes and the fatty acid synthase‐mediated de novo lipogenesis pathway. Maintaining the homeostasis of lipogenesis effectively prevents CRC aggravation and metastasis caused by Epstein–Barr virus infection.