MicroRNA-145 inhibits growth and migration of breast cancer cells through targeting oncoprotein ROCK1

Tumour Biol. 2016 Jun;37(6):8189-96. doi: 10.1007/s13277-015-4722-2. Epub 2015 Dec 29.

Abstract

MicroRNAs are small non-coding RNAs that may also function as oncogenes and tumor suppressor genes, as the abnormal expression of microRNAs is associated with various human tumors. MicroRNA-145 (miR-145) inhibits growth and increases chemo- or radiosensitivity in various cancers. However, the role of miR-145 in breast cancer progression remains unknown. In this study, miR-145 expression level was measured via quantitative real-time PCR in 88 pairs of human breast cancer tissues and adjacent normal tissues and in a panel of human breast cancer cell lines. Cell proliferation and cell migration were assessed by cell viability assay and transwell assay. Western blot was used to verify Rho-associated protein kinase 1 (ROCK1) as a novel target gene of miR-145. Our results showed that miR-145 was frequently downregulated in breast cancer tissues and cell lines. Overexpression of miR-145 in MCF-7 and BT-549 cell lines significantly inhibited cell proliferation, migration, and invasion in vitro. ROCK1 was identified as a target of miR-145, and ectopic expression of miR-145 downregulated ROCK1. Our findings indicate that miR-145 acts as a tumor suppressor and its downregulation in tumor tissues may contribute to the progression of breast cancer through a mechanism involving ROCK1, suggesting miR-145 as a potential new diagnostic and therapeutic target for the treatment of breast cancer.

Keywords: Breast cancer; MiR-145; Migration; Proliferation; ROCK1.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Blotting, Western
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology*
  • Case-Control Studies
  • Cell Movement*
  • Cell Proliferation*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunoenzyme Techniques
  • Lymphatic Metastasis
  • MicroRNAs / genetics*
  • Neoplasm Staging
  • Prognosis
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Tumor Cells, Cultured
  • rho-Associated Kinases / genetics
  • rho-Associated Kinases / metabolism*

Substances

  • 3' Untranslated Regions
  • Biomarkers, Tumor
  • MIRN145 microRNA, human
  • MicroRNAs
  • RNA, Messenger
  • ROCK1 protein, human
  • rho-Associated Kinases