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多聚胞嘧啶RNA结合蛋白1(PCBP1)增强原肌球蛋白3(TPM3)mRNA稳定性以促进食管鳞状细胞癌进展。

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

作者信息

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

机构信息

Department of Thoracic Surgery, Fujian Medical University Union Hospital, Fuzhou, China.

Department of Otolaryngology, Fujian Medical University Union Hospital, Fuzhou, China.

出版信息

Bioengineered. 2022 Apr;13(4):8581-8592. doi: 10.1080/21655979.2022.2053801.

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.

摘要

食管鳞状细胞癌(ESCC)的分子病因尚未完全阐明。了解ESCC的分子机制并寻找新的治疗靶点至关重要。多聚胞嘧啶RNA结合蛋白1(PCBP1)是一种RNA结合蛋白。在这里,我们通过定量聚合酶链反应(qPCR)和蛋白质免疫印迹分析发现食管癌组织中PCBP1表达上调。敲低PCBP1可显著减弱ESCC细胞的迁移和侵袭能力。机制上,PCBP1直接与原肌球蛋白3(TPM3)mRNA结合,这通过RNA-蛋白质免疫沉淀(RIP)试验得到验证。敲低PCBP1可显著降低TPM3的信使核糖核酸(mRNA)水平。在用放线菌素D(ActD)抑制细胞内mRNA合成后,发现敲低PCBP1可导致TPM3 mRNA降解显著减少。此外,PCBP1通过直接结合TPM3 mRNA的3'非翻译区(3'UTR)促进食管癌细胞的迁移和侵袭,增加TPM3 mRNA的稳定性。综上所述,在食管鳞状细胞癌中,PCBP1作为一种促癌因子,通过直接结合TPM3 mRNA的3'UTR增强TPM3 mRNA的稳定性。我们的研究结果为理解食管癌发生的分子机制提供了新的视角,并且PCBP1是一个有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6a00/9161940/1cc3741b9696/KBIE_A_2053801_UF0001_OC.jpg

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