Knockdown circTRIM28 enhances tamoxifen sensitivity via the miR-409-3p/HMGA2 axis in breast cancer

Reprod Biol Endocrinol. 2022 Sep 30;20(1):146. doi: 10.1186/s12958-022-01011-3.

Abstract

Background: Tamoxifen (TAM) is a frequently-used treatment for breast cancer (BC). But the TAM resistance seriously affects the patient therapeutic effect. Previous research indicated that circular RNAs (circRNAs) might participate in the regulatory processes of BC. Here, we discovered the parts of circular RNA tripartite motif-containing 28 (circTRIM28) in BC.

Methods: CircTRIM28, microRNA-409-3p (miR-409-3p), and high mobility group AT-hook 2 (HMGA2) levels were perceived by qRT-PCR and western blot. Moreover, the biological functions of the cells were examined. Furthermore, dual-luciferase report was employed to reconnoiter the targeted relationship between miR-409-3p and circTRIM28 or HMGA2.

Results: CircTRIM28 and HMGA2 were augmented, and the miR-409-3p was repressed in BC. Silencing circTRIM28 enhanced tamoxifen sensitivity and cell apoptosis, whereas hampered cell development in BC cells. In mechanism, circTRIM28 could sponge miR-409-3p to increase HMGA2. In addition, silencing circTRIM28 impeded tumor growth.

Conclusion: CircTRIM28 facilitated the BC via miR-409-3p/HMGA2.

Keywords: Breast cancer; HMGA2; Tamoxifen; circTRIM28; miR-409-3p.

MeSH terms

  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Proliferation / genetics
  • Female
  • Gene Expression Regulation, Neoplastic
  • HMGA2 Protein / metabolism
  • Humans
  • MicroRNAs* / genetics
  • RNA, Circular / genetics
  • Tamoxifen / pharmacology
  • Tamoxifen / therapeutic use

Substances

  • HMGA2 Protein
  • HMGA2 protein, human
  • MIRN409 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • Tamoxifen