TP53 mediated miR-3647-5p prevents progression of cervical carcinoma by targeting AGR2

Cancer Med. 2019 Oct;8(13):6095-6105. doi: 10.1002/cam4.2507. Epub 2019 Aug 22.

Abstract

Previous studies have shown that miRNAs involved in a number of biological processes, such as cell growth, development, differentiation, and apoptosis. The dysregulation of miRNA expression is associated with various diseases, including cervical cancer. However, the involvement of miR-3647-5p in the progression of tumors is unclear. In this study, we confirmed that miR-3647-5p was down-regulated during cervical carcinogenesis and development, which was positively correlated with the prognosis of patients with cervical cancer. In addition, our study showed that miR-3647-5p can inhibit the proliferation of cervical cancer cells and promote apoptosis, suggesting that miR-3647-5p is involved in the development of cervical cancer as a tumor suppressor gene. Furthermore, we found that transcription factor TP53 could promote the expression of miR-3647-5p, suggesting that the dysfunction of miR-3647-5p in cervical cancer may be related to TP53. In addition, we also found that miR-3647-5p can inhibit the proliferation of cervical cancer cells and promote apoptosis by targeting AGR2. In summary, our research reveals that transcription factor TP53 promotes the expression of miR-3647-5p, while up-regulated miR-3647-5p targets AGR2, inhibiting cervical cancer cell proliferation and promoting apoptosis. Our study reveals the mechanism of TP53/miR-3647-5p/AGR2 axis in cervical cancer, which may be useful for targeted therapy of cervical cancer.

Keywords: AGR2; TP53; cervical cancer; miR-3647-5p.

MeSH terms

  • Apoptosis
  • Cell Line
  • Disease Progression
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mucoproteins / genetics*
  • Mucoproteins / metabolism
  • Oncogene Proteins / genetics*
  • Oncogene Proteins / metabolism
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / metabolism

Substances

  • AGR2 protein, human
  • Mucoproteins
  • Oncogene Proteins
  • TP53 protein, human
  • Tumor Suppressor Protein p53