Expression of miRNAs Targeting mTOR and S6K1 Genes of mTOR Signaling Pathway Including miR-96, miR-557, and miR-3182 in Triple-Negative Breast Cancer

Appl Biochem Biotechnol. 2018 Dec;186(4):1074-1089. doi: 10.1007/s12010-018-2773-8. Epub 2018 Jun 4.

Abstract

Triple-negative breast cancer (TNBC) is a highly aggressive form of breast cancer. Aberrant expression of genes in mTOR pathway and their targeting miRNAs plays an important role in TNBC. The aim of this study was to determine the expression of mTOR and S6K1 and their targeting miRNAs in breast cancer cell lines and clinical samples. miRNAs targeting 3'-UTR of mTOR and S6K1 mRNAs were predicted using bioinformatic algorithms. MDA-MB-231, MCF-7, and MCF-10A as well as 20 TNBC samples were analyzed for gene and miRNA expression using quantitative real-time PCR (RT-qPCR). A receiver operating characteristic (ROC) curve analysis was performed for evaluation of candidate miRNAs as diagnostic biomarkers. miR-96 and miR-557 targeting mTOR and S6K1 mRNAs, respectively, were selected, and miR-3182 was selected as the miRNA targeting both genes. The miRNAs were down-regulated in cell lines, while their target mRNAs were up-regulated. Similar findings were observed in clinical samples. The ROC curve analysis revealed decline in expression of these miRNAs. We suggest that miR-96, miR-557, and miR-3182 can be used as inhibitory agents for mTOR and S6K1 in TNBC-targeted therapy.

Keywords: Breast cancer; S6K1; TNBC; mTOR; miR-3182; miR-557; miR-96.

MeSH terms

  • Female
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • MCF-7 Cells
  • MicroRNAs / biosynthesis*
  • MicroRNAs / genetics
  • Neoplasm Proteins / biosynthesis*
  • Neoplasm Proteins / genetics
  • RNA, Neoplasm / biosynthesis*
  • RNA, Neoplasm / genetics
  • Ribosomal Protein S6 Kinases, 70-kDa / biosynthesis*
  • Ribosomal Protein S6 Kinases, 70-kDa / genetics
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / biosynthesis*
  • TOR Serine-Threonine Kinases / genetics
  • Triple Negative Breast Neoplasms / genetics
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / therapy

Substances

  • MIRN557 microRNA, human
  • MIRN96 microRNA, human
  • MicroRNAs
  • Neoplasm Proteins
  • RNA, Neoplasm
  • MTOR protein, human
  • Ribosomal Protein S6 Kinases, 70-kDa
  • TOR Serine-Threonine Kinases
  • ribosomal protein S6 kinase, 70kD, polypeptide 1