Downregulation of MPC1 promotes HCC cell proliferation and metastasis via the STAT3 pathway

Abstract

Hepatocellular carcinoma (HCC) is prevalent globally, and the discovery of new targets is vital for the treatment of HCC. Mitochondrial pyruvate carrier 1 (MPC1) has been found to exhibit reduced expression and promote tumour progression in some cancers, although its role in HCC needs to be explored. Using GEO datasets and Kaplan‒Meier plotter, the clinicopathological features and patient prognosis were analysed by assessing the expression levels of MPC1 in HCC tissues. After MPC1-knockdown and MPC1-overexpressing cell lines were constructed, the effects of modulating MPC1 expression on the malignant phenotype of HCC cells were tested via CCK8, colony formation, and scratch assays and flow cytometry. The effects of MPC1 on HCC cells and mitochondria were examined via MitoTracker Red CMXRos staining, cytoskeleton staining and cellular energy metabolism assays. MPC1 expression was found to be reduced in HCC patients and correlated with prognosis and clinicopathological features. It was found that low expression of MPC1 promotes the malignant phenotype of HCC cells and affects the mitochondrial energy metabolism of HCC cells to support the tumour microenvironment, and that MPC1 may act through signal transducer and activator of transcription 3 (STAT3). MPC1 might play a tumor-suppressing role in HCC through its interaction with STAT3, and this discovery could offer novel perspectives for HCC treatment.