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

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.

Keywords: PCBP1; TPM3; esophageal squamous cell carcinoma (ESCC); mRNA stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions
  • Carcinogenesis / genetics
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • DNA-Binding Proteins* / genetics
  • Esophageal Neoplasms* / metabolism
  • Esophageal Squamous Cell Carcinoma* / genetics
  • Esophageal Squamous Cell Carcinoma* / pathology
  • Humans
  • RNA Stability
  • RNA, Messenger / genetics
  • RNA-Binding Proteins* / genetics
  • Tropomyosin* / genetics

Substances

  • 3' Untranslated Regions
  • DNA-Binding Proteins
  • PCBP1 protein, human
  • RNA, Messenger
  • RNA-Binding Proteins
  • TPM3 protein, human
  • Tropomyosin

Grants and funding

This work was supported by the Fujian Medical University under Grant Funding from Fujian Medical University 2018QH1037.