PRDM16 inhibits cell proliferation and migration via epithelial to mesenchymal transition by directly targeting pyruvate carboxylase in papillary thyroid cancer

Abstract

Background PRDM16 (known as MEL1), a member of PR domain zinc finger family, has been implicated in multiple biological processes including cancers. It is not clearly yet whether PRDM16 is involved in tumor progress of papillary thyroid cancer (PTC). Methods We identified PRDM16 expression level in PTC tissues by qRT-PCR and analyzed its relationship with clinical characteristics in both Fudan University Shanghai Cancer Center (FUSCC) cohort and TCGA cohort. We tested the function of PRDM16 in PTC cells both in vivo and in vitro. We found direct downstream target of PRDM16, pyruvate carboxylase (PC) by RNA-sequencing, rescue experiments, Luciferase assay and Chromatin Immunoprecipitation assay. Results PRDM16 was downregulated in papillary thyroid cancer tissues and was significantly related with lymph node metastases and extrathyroid extension in both FUSCC and TCGA cohorts. Overexpression of PRDM16 could attenuate proliferation and migration of PTC cells via inhibiting epithelial to mesenchymal transition process. PC was upregulated in papillary thyroid cancer tissues. Knockdown of PC could inhibit proliferation and migration in TPC-1 and K1 cells. The repression effect on cell proliferation and migration from PRDM16 was PC dependent. PRDM16 could directly bind to PC promoter and inhibited its expression at transcription level. Moreover, the mRNA expression level of PRDM16 and PC was negatively related in human PTC tissues. Conclusions In conclusion, PRDM16 exhibited anti-tumor effect and EMT inhibition function in PTC by directly binding with PC promoter. PRDM16 may be a novel therapeutic target in papillary thyroid cancer.