Objectives: Paraneoplastic antigen Ma family (PNMA) is dysregulated in the pathological development of various cancers. However, the actions of PNMA member 5 (PNMA5) in cancers are still unknown. The aim of this study was to explore the biological actions of PNMA5 and its implication in epithelial-mesenchymal transition (EMT) during the progression of colorectal cancer (CRC).
Methods: Immunohistochemical staining, western blot and qPCR were used to explore PNMA5 expression in colorectal cancer tissues and cells. In addition, western blot, MTT assays, Colony formation assay, wound-healing, and transwell cell invasion assays were used to investigate the effects of PNMA5 on EMT in colorectal cancer. The lung metastasis models and xenografts in nude mice were established to explore the roles of PNMA5 in vivo.
Results: It was found that the expression level of PNMA5 in colorectal cancer tissues was significantly up regulated compared to that in the adjacent tissues. The overall survival rates of patients with a higher PNMA5 expression were markedly decreased. In addition, knockdown of PNMA5 expression decreased the proliferation, invasion and migration of both HCT-15 and HCT-116 cells. PNMA5 expression was found to be positively associated with the expression of C-myc, CyclinD1, Ki67, N-cadherin, zinc finger E-box binding homeobox 1 and vimentin, and negatively associated with E-cadherin. It was also found that PNMA5 knockdown attenuated TGF-β-induced EMT in colorectal cancer cells. Finally, it was demonstrated that PNMA5 accelerated colorectal cancer cell proliferation, invasion and migration in vivo.
Conclusion: The results revealed that PNMA5 increased cellular proliferation, invasion and migration in colorectal cancer. PNMA5 plays a key role in promoting CRC carcinogenesis and progression for patients with CRC.
Keywords: EMT; PNMA5; colorectal cancer; proliferation.
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