PolyC-RNA-binding protein 1 (PCBP1) enhances tropomyosin 3 (TPM3) mRNA stability to promote the progression of esophageal squamous cell carcinoma

PolyC-RNA结合蛋白1(PCBP1)增强原肌球蛋白3(TPM3)mRNA稳定性,促进食管鳞状细胞癌进展

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作者:Kaiming Peng, Xiaoqiang Chen, Anqin Lin, Zhangwei Tong, Wenwei Lin

Abstract

The molecular etiology of esophageal squamous cell carcinoma (ESCC) has not been fully elucidated. Understanding the molecular mechanisms and finding new therapeutic targets for ESCC are of crucial importance. PolyC-RNA-binding protein 1 (PCBP1) is an RNA-binding protein. Here, we found overexpressed PCBP1 in esophageal cancer tissues by quantitative polymerase chain reaction (qPCR) and western blotting analysis. PCBP1 knockdown significantly attenuated migratory and invasion abilities of ESCC cells. Mechanistically, PCBP1 bound directly to tropomyosin 3 (TPM3) mRNA, which was verified by RNA-protein immunoprecipitation (RIP) assay. PCBP1 knockdown markedly reduced messenger RNA (mRNA) levels of TPM3. After inhibiting intracellular mRNA synthesis with actinomycin D (ActD), it was found that PCBP1 knockdown contributed to a significant decrease in TPM3 mRNA degradation. Furthermore, PCBP1 promoted migration and invasion of EC cells by directly binding to the 3'UTR of TPM3 mRNA, increasing TPM3 mRNA stability. Taken together, PCBP1 acting as a pro-oncogenic factor enhances TPM3 mRNA stability by directly binding to the 3'UTR of TPM3 mRNA in esophageal squamous cell carcinoma. Our findings provide a new perspective for understanding the molecular mechanism of esophageal carcinogenesis, and PCBP1 is a promising therapeutic target.

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