MiR-140-5p inhibits cell proliferation and metastasis by regulating MUC1 via BCL2A1/MAPK pathway in triple negative breast cancer

Cell Cycle. 2019 Oct;18(20):2641-2650. doi: 10.1080/15384101.2019.1653107. Epub 2019 Aug 14.

Abstract

Noncoding RNAs play important roles in the progression of malignant tumors, including triple negative breast cancer (TNBC). Accumulating evidence supported the involvement of the oncogenic MUC1 in tumor metastasis. Our study aimed to explore the roles of miR-140-5p and MUC1 in TNBC and identify the potential underlying mechanisms. In the present study, we found that miR-140-5p expression was significantly decreased in TNBC tissues and associated with advanced clinical features and poor prognosis. MiR-140-5p overexpression suppressed TNBC cells proliferation, invasion ability in vitro and reduced tumor growth in vivo. Subsequently, MUC1 was verified to be a direct target of miR-140-5p in TNBC. Furthermore, we revealed that MUC1 could regulate MAPK pathway through regulating BCL2A1 expression in TNBC. Thus, our study indicated that miR-140-5p might regulate MUC1 to suppress TNBC cells proliferation and metastasis by regulating BCL2A1/MAPK pathway, suggesting miR-140-5p could serve as a potential therapeutic target for TNBC.

Keywords: BCL2A1; MUC1; Mir-140-5p; TNBC.

Publication types

  • Retracted Publication

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Disease-Free Survival
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Heterografts
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Minor Histocompatibility Antigens / metabolism*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Mucin-1 / metabolism*
  • Neoplasm Invasiveness / genetics
  • Prognosis
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Transfection
  • Triple Negative Breast Neoplasms / metabolism*
  • Triple Negative Breast Neoplasms / pathology
  • Triple Negative Breast Neoplasms / secondary
  • Tumor Burden / genetics

Substances

  • BCL2-related protein A1
  • MUC1 protein, human
  • MicroRNAs
  • Minor Histocompatibility Antigens
  • Mirn140 microRNA, human
  • Mucin-1
  • Proto-Oncogene Proteins c-bcl-2
  • Mitogen-Activated Protein Kinases