NR1D2 Accelerates Hepatocellular Carcinoma Progression by Driving the Epithelial-to-Mesenchymal Transition

INTRODUCTION: A poor prognosis owing to cancer invasion and metastasis, hepatocellular carcinoma (HCC) is one of the leading causes of malignancy deaths worldwide. A dominant epithelial-to-mesenchymal transition or EMT function in tumour metastasis is substantially evidenced. Prior reports identified a likely correlation of the nuclear hormone receptor NR1D2 with HCC progression, but the underlying molecular mechanisms and role of invasion and metastasis are still to be adequately documented. METHODS: We carried out PROGgeneV2 platform database analysis and compared NR1D2 expression in HCC tissues with that in adjacent noncancerous tissues by Western blotting. Cell proliferation, invasion, and migration were also assessed using a lentivirus system. Moreover, the relevant signalling proteins were evaluated. RESULTS: The PROGgeneV2 platform database analysis suggested an upregulated NR1D2 expression related to poor overall survival, or OS, in HCC, with higher levels in HCC, compared to the adjoining non-cancerous tissue. Depleting NR1D2 decreased HCC cell proliferation, migration and invasion in vitro, whilst in vivo downregulation revealed fewer metastatic nodules in the lungs. Furthermore, NR1D2 knockdown amplified epithelial marker, namely E-cadherin expressions, and decreased mesenchymal markers, ie, N-cadherin and vimentin expressions, with β-catenin overexpression. CONCLUSION: NR1D2 is shown to accelerate HCC progression via driving EMT.