Knockdown expression of <i>MECR</i>, a novel gene of mitochondrial FAS II inhibits growth and colony-formation, promotes apoptosis of hepatocelluar carcinoma cells

Abstract

Mitochondrial trans-2-enoyl-CoA reductase (MECR) is a protein-coding gene, and the protein encoded by this gene is an oxidoreductase that catalyzes the last step in mitochondrial fatty acid synthesis (mtFASII). Numerous studies have shown disorder of lipid metabolism is closely related with malignance, especially in liver cancer. Through pre-experiment, we found that the expression of MECR gene was highly expressed in hepatocelluar carcinoma (HCC) cell lines in vitro. This suggests that the MECR gene may play a role of oncogene in HCC. Therefore, we conducted a preliminary experimental study on the role of MECR gene in HCC cells in vitro. Objective to explore whether the MECR gene can affect the malignant biological behavior of HCC. We selected HCC cell line BEL-7404 as experimental cell, which involves the highest expression of MECR in the pre-experiment. We constructed MECR knockdwon lentivirus vector, and then infected HCC cell lines to down-regulate MECR expression, and establish negative control group (NC). Through various experiments of cytology, our study showed that knockdown of MECR inhibited cell proliferation and colony formation, promoted apoptosis, and inhibited metastasis in HCC cell lines BEL-7404. MECR might serve as a novel gene therapeutic target for the treatment of HCC. Further study is needed to elucidate the signaling pathway through which MECR functions in HCC.

Remodelin, a N‐acetyltransferase 10 (NAT10) inhibitor, alters mitochondrial lipid metabolism in cancer cells

“…Alteration in cell metabolism is an established hallmark of cancer 25 . Often cancer cells utilize multiple pathways and mechanisms involving different metabolites to support their survival, evade tissues and metastasis 25,26 . Lipid metabolism is altered by cancer cells transforming into malignant phenotype.…”

“…Our data showed that Remodelin modulates MFAE and beta oxidation by decreasing levels MECR and ECHS1 . Both genes were shown to be overexpressed in cancer cells as numerous cancers utilize these genes to promote cell survival, cell proliferation, and metastasis through the accumulation of lipids 26,28‐30 . Although ECHS1 deficiency is shown to reduce lipid accumulation, and other studies in renal cancer reported that the presence of ECHS1 inactivates FAS, hence, increasing lipid accumulation 29‐31 .…”

“…Therefore, it is a double‐edged sword since it participates in both MFAE and beta oxidation (Figures 3 and 4). However, MECR is specifically known to mediate FAS 26,28 . Numerous studies have reported the role of MECR in promoting cancer cell survival, 26 cardiac dysfunction, 32 neurodegeneration and placental development 33 .…”

Mitochondrial fatty acid synthesis coordinates oxidative metabolism in mammalian mitochondria

“…Knockout of the mitochondrial 2-enoyl thioester reductase, Mecr , is lethal in mice due to a placental defect ( Nair et al, 2017 ), while the inducible knockout of Mecr specifically in Purkinje cells leads to loss of this cell population and recapitulates many phenotypes of MePaN syndrome, the human disease caused by Mecr mutation ( Gorukmez et al, 2019 ; Heimer et al, 2016 ; Nair et al, 2018 ). Similarly, Mecr knockdown has been shown to inhibit the growth of hepatocellular carcinoma cells ( Cai et al, 2019 ). While these detrimental phenotypes are clear, the molecular consequences of mtFAS loss remain poorly understood.…”

Identification and validation of hub genes for diabetic retinopathy

“…In the livers of mice with liver fibrosis, MECR as lipoic acid synthetic pathway enzymes were significantly reduced ( Luo & Shen, 2020 ). Moreover, MECR is reportedly crucial in many diseases, such as hepatocelluar carcinoma ( Cai et al, 2019 ), childhood-onset dystonia and optic atrophy ( Heimer et al, 2016 ). Meanwhile, a marked body of evidence from both cohort and case-control studies have indicated the significant relevance between the disorder of lipid levels and DR ( Das et al, 2015 ).…”