MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway

• Published in: Scientific reports 2017-02, Vol.7 (1), p.41942-41942, Article 41942
• Main Authors: Miao, Yuan, Zheng, Wei, Li, Nana, Su, Zhen, Zhao, Lifen, Zhou, Huimin, Jia, Li
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; 13/1; 13/109; 13/31; 13/89; 631/154; 631/80/458; 82/51; 82/80; AKT protein; Animals; Apoptosis; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Case-Control Studies; Cell Proliferation; Chemoresistance; Cytotoxicity; Drug resistance; Drug Resistance, Neoplasm - genetics; Female; Follow-Up Studies; Gene Expression Regulation, Neoplastic; Humanities and Social Sciences; Humans; Mice; Mice, Nude; MicroRNAs; MicroRNAs - genetics; miRNA; multidisciplinary; Multidrug resistance; Overexpression; Phosphatidylinositol 3-Kinases - genetics; Phosphatidylinositol 3-Kinases - metabolism; Prognosis; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; PTEN Phosphohydrolase - genetics; PTEN Phosphohydrolase - metabolism; PTEN protein; Science; Signal transduction; Tumor cell lines; Tumor Cells, Cultured; Xenograft Model Antitumor Assays
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep41942

Multidrug resistance (MDR) correlates with treatment failure and poor prognosis among breast cancer patients. This study was aimed to investigate the possible mechanism by which microRNA-130b-3p (miR-130b) mediates the chemoresistance and proliferation of breast cancer. MiR-130b was found to be up-regulated in tumor tissues versus adjacent tissues of breast cancer, as well as in adriamycin (ADR) resistant breast cancer cell line (MCF-7/ADR) versus its parental line (MCF-7) and the non-malignant breast epithelial cell line (MCF-10A), demonstrating its crucial relevance for breast cancer biology. We identified that PTEN was a direct target of miR-130b and inversely correlated with miR-130b expression in breast cancer. Moreover, over-expression of miR-130b promoted drug resistance, proliferation and decreased apoptosis of MCF-7 cells, while suppression of miR-130b enhanced drug cytotoxicity and apoptosis, as well as reduced proliferation of MCF-7/ADR cells in vitro and in vivo. Particularly, miR-130b mediated the activity of phosphoinositide-3 kinase (PI3K)/Akt signaling pathway as well as the chemoresistance and proliferation of breast cancer cell lines, which was partially blocked following knockdown of PTEN. Altogether, miR-130b targets PTEN to induce MDR, proliferation, and apoptosis via PI3K/Akt signaling pathway. This provides a novel promising candidate for breast cancer therapy.