Hepatocellular carcinoma (HCC) is leading cause of tumor-related deaths worldwide. The intracellular chloride channel protein (CLIC1) plays a role in the occurrence and progression of HCC, although the underlying mechanisms are still unclear. We evaluated the CLIC1 mRNA and protein levels in both patient tissues and HCC cell lines, and analyzed the correlation between CLIC1 expression and clinical features. The biological function of CLIC1 in HCC was examined in vivo and in vitro. The upstream regulatory factors were identified by bioinformatics programs, and downstream mechanisms affecting HCC behavior have also been explored and validated. CLIC1 was up-regulated in HCC tissues and cell lines, and promoted the proliferation, invasion and migration of HCC cells in vivo and in vitro. TP53 was identified as the upstream transcription factor of CLIC1. MiR-122-5p also regulated CLIC1 levels by degrading the transcripts. More importantly, we found that the increased CLIC1 was significantly related to the activation of MYC signaling. By binding with MYC, CLIC1 enhanced the transcription activity of MYC to downstream genes, rather than by altering its expression. Finally, a positive feedback regulatory loop between CLIC1 and MYC was established. CLIC1 is closely related to the occurrence, progression and prognosis of HCC, and a promising novel therapeutic target.
Keywords: CLIC1; Hepatocellular carcinoma; MYC; TP53; miR-122-5p.
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