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Depletion of C12orf48 inhibits gastric cancer growth and metastasis via up-regulating Poly r(C)-Binding Protein (PCBP) 1

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Background Gastric cancer remains a major cause of cancer-related death worldwide. C12orf48, also named PARP1 binding protein, is over-expressed in several cancers. However, the expression profile and potential roles of… Click to show full abstract

Background Gastric cancer remains a major cause of cancer-related death worldwide. C12orf48, also named PARP1 binding protein, is over-expressed in several cancers. However, the expression profile and potential roles of C12orf48 in gastric cancer are largely unknown. Methods We used bioinformatics approaches and tissue microarray immunohistochemistry to analyze the expression profile of C12orf48 in gastric cancer tissues. Plasmid-mediated over-expression or knockdown were performed. CCK-8 assays and flow cytometry were employed to evaluate cellular proliferation and apoptosis respectively. Transwell assays were used to assess migrative and invasive abilities. The roles of C12orf48 were also evaluated in a xenograft tumor model. Results We found that C12orf48 was over-expressed in gastric cancer tissue, which associated with advanced stage and poor prognosis. In vitro and in vivo experiments showed depletion of C12orf48 attenuated cancer growth, while facilitated apoptosis. Further, the expression of Poly r(C)-Binding Protein (PCBP) 1 was found negatively regulated by C12orf48. Intended up-regulation of PCBP1 prevented C12orf48-mediated proliferation and rescued cells from apoptosis. Besides, C12orf48 promoted cellular migration and invasion, with E-cadherin down-regulated while vimentin and N-cadherin up-regulated, which was reversed by up-regulated PCBP1. Conclusions Our findings indicate that depletion of C12orf48 inhibited gastric cancer growth and metastasis via up-regulating PCBP1. Targeting C12orf48-PCBP1 axis may be a potential therapeutic strategy.

Keywords: cancer; binding protein; depletion c12orf48; c12orf48; cancer growth; gastric cancer

Journal Title: BMC Cancer
Year Published: 2022

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