miR-27b-3p inhibits proliferation and potentially reverses multi-chemoresistance by targeting CBLB/GRB2 in breast cancer cells

Cell Death Dis. 2018 Feb 7;9(2):188. doi: 10.1038/s41419-017-0211-4.


Drug resistance remains a major problem in the treatment of conventional chemotherapeutic agents in breast cancers. Owing to heterogeneity and complexity of chemoresistance mechanisms, most efforts that focus on a single pathway were unsuccessful, and exploring novel personalized therapeutics becomes urgent. By a system approach, we identified that microRNA-27b-3p (miR-27b), a miRNA deleted in breast cancer tissues and cell lines, has a master role in sensitizing breast cancer cells to a broad spectrum of anticancer drugs in vitro and in vivo. Mechanistic analysis indicated that miR-27b enhanced responses to PTX by directly targeting CBLB and GRB2 to inactivate both PI3K/Akt and MAPK/Erk signaling pathways. Further, miR-27b was identified as a promising molecular biomarker in chemoresistance, clinicopathological features, and prognosis for breast cancer patients. In conclusion, we propose that combinational use of miR-27b and chemotherapeutic agents might be a promising therapeutic strategy to increase long-term drug responses in breast cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / biosynthesis
  • Adaptor Proteins, Signal Transducing / genetics*
  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Down-Regulation
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Female
  • GRB2 Adaptor Protein / biosynthesis
  • GRB2 Adaptor Protein / genetics*
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Mice
  • Mice, Nude
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Paclitaxel / pharmacology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphoinositide-3 Kinase Inhibitors
  • Proto-Oncogene Proteins c-akt / antagonists & inhibitors
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-cbl / biosynthesis
  • Proto-Oncogene Proteins c-cbl / genetics*


  • Adaptor Proteins, Signal Transducing
  • Antineoplastic Agents, Phytogenic
  • GRB2 Adaptor Protein
  • GRB2 protein, human
  • MIRN27 microRNA, human
  • MicroRNAs
  • Phosphoinositide-3 Kinase Inhibitors
  • CBLB protein, human
  • Proto-Oncogene Proteins c-cbl
  • Proto-Oncogene Proteins c-akt
  • Paclitaxel