miR-145 Inhibits Mitochondrial Function of Ovarian Cancer by Targeting ARL5B

Abstract

Metabolic reprogramming refers to the transformation of the whole metabolic network including glycolysis and mitochondrial metabolism, mainly manifested in Warburg effect and mitochondrial metabolic reprogramming. The roles of miR-145 in glycolysis have been established in ovarian cancer cells. Howerer, its roles in mitochondrial metabolic reprogramming are still unclear. This study aims to identify whether miR-145 regulates mitochondrial metabolic reprogramming in ovarian cancer cells. First, functional experiment showed that overexpression of miR-145 inhibited mitochondrial function in ovarian cancer cells, evident by the decreased mtDNA copy numbers, ATP level, mitochondrial membrane potential, and the expression levels of mitochondrial markers. Mechanistically, miR-145 inhibited mitochondrial function by targeting ARL5B directly. Futhermore, miR-145 overexpression decreased ARL5B expression in ovarian cancer tissue subcutaneous tumors of nude mice. In conclusion, we have highlighted that miR-145 inhibits mitochondrial function and achieves this by targeting ARL5B directly for the first time. The results provides a more adequate theoretical basis for understanding the molecular pathology of ovarian cancer, and provides the necessary basic data for miR-145 as a potential diagnosis and treatment target for ovarian cancer.

Targeting lactate metabolism and glycolytic pathways in the tumor microenvironment by natural products: A promising strategy in combating cancer

“…160 Another study showed that an important micro-RNA in the process of tumor development, miR-145, suppresses the Warburg effect and HK2 expression in the human ovarian cancer cell line (SKOV3) and subsequently decreases cancer progression. 162 Berberine promotes Tet Methylcytosine Dioxygenase 3 (TET3)-mediated demethylation of pre-miR-145 to increase inhibition of miR-145 on HK2. TET3 is a protein-coding gene that is located upstream of miR-145 and affects its gene expression.…”

“…The reduction in the HIF‐1α expression level decreases the transcription of glucose metabolism‐related genes such as GLUT1 , LDHA , and HK2 160 . Another study showed that an important micro‐RNA in the process of tumor development, miR‐145, suppresses the Warburg effect and HK2 expression in the human ovarian cancer cell line (SKOV3) and subsequently decreases cancer progression 162 . Berberine promotes Tet Methylcytosine Dioxygenase 3 (TET3)‐mediated demethylation of pre‐miR‐145 to increase inhibition of miR‐145 on HK2.…”