Up-regulation of MIC19 promotes growth and metastasis of hepatocellular carcinoma by activating ROS/NF-κB signaling.

ABSTRACT

BACKGROUND: Mitochondrial malfunction has been well-recognized as a critical step in the pathogenesis of many types of diseases, including cancer. MIC19 is a core a subunit of the MICOS complex that plays a critical role in maintaining the normal function of mitochondria. However, the biological functions of MIC19 in human hepatocellular carcinoma (HCC) remain unclear. METHODS: The expression level of MIC19 in HCC was evaluated by bioinformatics analysis, quantitative real-time PCR and immunohistochemistry staining assays. Cell growth and metastasis experiments were used to assess the biological functions of MIC19 in HCC cells. FINDINGS: MIC19 expression was frequently upregulated in both human HCC specimens and cell lines, and its upregulation is closely associated with patients' survival. Results from loss-of-function and gain-of-function experiments demonstrated that knockdown of MIC19 significantly attenuated, while overexpression of MIC19 enhanced, the proliferation, colony formation, migration and invasion abilities of HCC cells. Mechanistically, we found that MIC19 has no effect on mitochondrial energy production, while activated ROS/NF-κB signaling, which was required for MIC19-promoted HCC growth and metastasis. INTERPRETATION: Our findings suggest that MIC19 play a critical oncogenic role in HCC, implying that MIC19 may serve as a potential therapeutic target in the treatment of HCC.