miR-3929 Inhibits Proliferation and Promotes Apoptosis by Downregulating Cripto-1 Expression in Cervical Cancer Cells

Cytogenet Genome Res. 2021;161(8-9):425-436. doi: 10.1159/000518521. Epub 2021 Sep 20.

Abstract

Cripto-1 is highly expressed in many cancers, and downregulating its expression may become a promising approach for cancer treatment. However, the regulation of Cripto-1 expression is not well characterized. In this study, we focused on the post-transcriptional regulation of Cripto-1 expression and analyzed the potential miRNAs that bind to the 3'UTR of Cripto-1 mRNA. miR-3929 was found to be able to bind to the 3'UTR and downregulate the expression of Cripto-1 in cervical cancer cells. Then, we analyzed the effect of miR-3929 on the biological behavior of cervical cancer cells, finding that miR-3929 could reduce cell viability, DNA synthesis, and Ki67 expression and induce cell cycle arrest in the G2/M phase; overexpression of Cripto-1 reversed the inhibitory effect of miR-3929 on proliferation. Moreover, DAPI staining and flow cytometry revealed that miR-3929-induced cell apoptosis is dependent on the mitochondrial pathway; the overexpression of Cripto-1 reversed the proapoptotic effect of miR-3929. Finally, the in vivo results showed that miR-3929 significantly inhibits the growth of HeLa xenograft tumors in nude mice. Therefore, our findings suggest that miR-3929 inhibits the proliferation and induces the apoptosis of cervical cancer cells by downregulating Cripto-1 via specifically targeting the 3'UTR of its mRNA.

Keywords: Apoptosis; Cervical cancer; Cripto-1; Proliferation; miR-3929.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Animals
  • Apoptosis / genetics*
  • Cell Proliferation / genetics
  • Down-Regulation*
  • Female
  • GPI-Linked Proteins / genetics*
  • Gene Expression Regulation, Neoplastic*
  • HeLa Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics*
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Neoplasm Proteins / genetics*
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / pathology*
  • Xenograft Model Antitumor Assays

Substances

  • 3' Untranslated Regions
  • GPI-Linked Proteins
  • Intercellular Signaling Peptides and Proteins
  • MicroRNAs
  • Neoplasm Proteins
  • TDGF1 protein, human