MicroRNA-140-5p inhibits cellular proliferation, migration and invasion by downregulating AKT/STAT3/NF-κB pathway in breast carcinoma cells

Acta Pharm. 2022 Oct 18;72(4):587-597. doi: 10.2478/acph-2022-0039. Print 2022 Dec 1.

Abstract

MicroRNA-140-5p (miR-140-5p) plays a pivotal role in human cancers. However, its role and molecular mechanisms in breast carcinoma are not fully explored. Using miR-140-5p transfected breast cancer cell line MDA-MB-231, several in vitro experiments were performed and described in this paper. They consist of the cell proliferation assay, wound healing assay, transwell assay, colony formation assays and qRTPCR. Expression levels of target proteins were determined using Western blotting. In addition, experiments on animal models were performed to study the possible role of miR-140-5p in tumorigenesis of breast carcinoma cells. The induction of experimental breast tumor in mice model was achieved through the incorporation of MDA-MB-231 tumor cells subcutaneously into the middle left side of the mice. The results showed that miR-140-5p up-regulation significantly suppresses proliferation, cellular invasion and migration of breast carcinoma cells. Furthermore, miR-140-5p up-regulation stops breast cancer cells at G0/G1 phase. The results of the animal model indicated that up-regulation of miR-140-5p suppresses its tumorigenic ability. Moreover, we also found that miR-140-5p up-regulation reduces the phosphorylation level of STAT3, p65, and AKT. In addition, miR-140-5p overexpression significantly decreases CDK2 expression while increasing E-cadherin expression level. These data revealed that miR-140-5p suppressed tumor progression of breast carcinoma cells through inhibition of the AKT/STAT3/NF-κB pathway. Taken the present study results together, we can conclude that miR-140-5p may act as a novel target in microRNA-targeting anticancer strategy for the treatment of breast cancer.

Keywords: AKT/STAT3/NF-κB; breast cancer; cell proliferation; microRNA-140-5p; tumor progression.

MeSH terms

  • Animals
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • MDA-MB-231 Cells
  • Mice
  • MicroRNAs* / genetics
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism

Substances

  • MicroRNAs
  • Mirn140 microRNA, human
  • MIRN140 microRNA, mouse
  • NF-kappa B
  • Proto-Oncogene Proteins c-akt
  • STAT3 protein, human
  • STAT3 Transcription Factor