MicroRNA-130b targets PTEN to mediate drug resistance and proliferation of breast cancer cells via the PI3K/Akt signaling pathway.
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.
College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China.
Yuan
Y
Miao
Department of Central Laboratory, the First Affiliated Hospital of Dalian Medical University, Dalian 116011, Liaoning Province, China.
Wei
W
Zheng
College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China.
Nana
N
Li
Graduate School, Dalian Medical University, Dalian 116044, Liaoning Province, China.
Zhen
Z
Su
College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China.
Lifen
L
Zhao
Department of Microbiology, Dalian Medical University, Dalian 116044, Liaoning Province, China.
Huimin
H
Zhou
College of Laboratory Medicine, Dalian Medical University, Dalian 116044, Liaoning Province, China.
Li
L
Jia
D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D016022:Case-Control Studies; D049109:Cell Proliferation; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; C554019:MIRN130 microRNA, human; D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human