MCT4 Promotes Hepatocellular Carcinoma Progression by Upregulating TRAPPC5 Gene

Purpose: Monocarboxylate Transporter 4 (MCT4) is an important component of Cancer cell glycolytic metabolism. It has been confirmed that MCT4 is highly expressed in hepatocellular carcinoma (HCC) cells and tissues and is significantly associated with poor prognosis of HCC patients. However, research on its downstream molecules that affect HCC is still insufficient. The aim of current research was to investigate the MCT downstream molecule and its role of in HCC development.

Patients and methods: After MCT4 expression was knocked down by RNA interference, RNA sequencing and quantitative Real-Time PCR were used to screen for differentially expressed genes in an HCC cell line (HCCLM3). Immunohistochemistry in HCC tissue microarray was carried out to evaluate the Trafficking Protein Particle Complex Subunit 5 (TRAPPC5) expression. Cell proliferation, migration, and invasion were evaluated by CCK-8 assay, colony formation assay, transwell and wound-healing test, respectively. Xenograft experiment was employed to investigate the function of TRAPPC5 on tumor growth in vivo. Related signaling pathway proteins were evaluated by Western blot.

Results: TRAPPC5 expression was significantly downregulated after knocking down of MCT4 in HCCLM3. TRAPPC5 was highly expressed in HCC tissues, and it could enhance the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) process of HCC cells. In vivo experiment showed that TRAPPC5 could promote HCC tumorigenesis.

Conclusion: In the process of MCT4 affecting the progression of HCC, TRAPPC5 is one of the most important related molecules. TRAPPC5 suppression could significantly reduce HCC cell proliferation, migration and invasion and could serve as a therapeutic target in HCC.