Partition defective 3 promotes TAZ nuclear localization and promotes Amphiregulin transcription to promote liver hepatocellular carcinoma cell invasion, migration and epithelial mesenchymal

Abstract

Abstract Background Partition defective 3 (PARD3) regulates cell polarity and functions as a cancer promoting or tumor suppressor in different cancer types. PARD3 was reported to be highly expressed in liver hepatocellular carcinoma (LIHC) tissues and high expression of PARD3 was significantly associated with poor clinicopathological features and lower overall survival, but whether PARD3 regulated invasion, migration and epithelial mesenchymal transition (EMT) in LIHC has not been reported. Objectives To investigate the effect and mechanism of PARD3 on LIHC cell invasion, migration and EMT. Methods PARD3 expression in LIHC tumor group and relationship with survival were queried according to the GEPIA website. PARD3 mRNA and protein expression in 41 clinical samples were determined by RT-qPCR and immunohistochemistry (IHC), respectively. PARD3, transcriptional coactivator with PDZ-binding motif (TAZ)and amphiregulin ༈AREG༉expression in HepG2 cells with overexpression or knockdown, and the expression of PARD3, TAZ, AREG and EMT related proteins were determined by Western blot. Transwell assay for HepG2cell invasion ability. The migration ability of HepG2 cells was detected by wound healing experiments. TAZ localization was detected by immunofluorescence. Co-IP detected the effect of PARD3 on TAZ and TAZ TEAD binding. The effect of TAZ on AREG transcript levels was examined by RT-qPCR. Results PARD3 was found to be highly expressed in LIHC tumor group by GEPIA website query, and the expression of PARD3 gradually increased with increasing tumor stage, and high expression of PARD3 usually means low overall survival in LIHC. We also found that PARD3 was highly expressed in LIHC tissues. Knockdown of PARD3 inhibited HepG2 cell invasion, migration and EMT, while overexpression of PARD3 played the opposite role. Moreover, PARD3 promotes AREG transcription by promoting TAZ nuclear localization, which in turn promotes LIHC cell invasion, migration and EMT. Conclusion PARD3 promotes TAZ nuclear localization and promotes AREG transcription to promote epithelial mesenchymal transition in LIHC.