MiR-26a inhibits proliferation and migration of breast cancer through repression of MCL-1

• Published in: PloS one 2013-06, Vol.8 (6), p.e65138
• Main Authors: Gao, Jie, Li, Laisheng, Wu, Minqing, Liu, Min, Xie, Xinhua, Guo, Jiaoli, Tang, Hailin, Xie, Xiaoming
• Format: Article
• Language: English
• Subjects: Adult; Animals; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Base Sequence; Bcl-2 protein; Biology; Breast cancer; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cancer; Cancer therapies; Carcinogenesis; Carcinogens; Cell cycle; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell Movement - genetics; Cell proliferation; Cell Proliferation - drug effects; Cell Survival - drug effects; Cell Survival - genetics; Chemotherapy; Down-Regulation - drug effects; Down-Regulation - genetics; Ectopic expression; Female; Gene expression; Health aspects; Humans; Laboratories; Leukemia; Liver cancer; Lung cancer; Mcl-1 protein; Medical prognosis; Medicine; Metastasis; MicroRNA; MicroRNAs; MicroRNAs - genetics; Middle Aged; miRNA; Myeloid Cell Leukemia Sequence 1 Protein - genetics; Nucleotides; Oncology; Paclitaxel; Paclitaxel - pharmacology; Post-transcription; Prostate; Ribonucleic acid; RNA; Studies; Transcription (Genetics); Tumor cell lines; Tumor suppressor genes; Tumorigenesis
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0065138

Breast cancer is the most commonly malignancies in women. MicroRNAs are a family of small non-coding RNAs 18-25 nucleotides in length that post-transcriptionally modulate gene expression. MiR-26a has been reported as a tumor suppressor microRNA in breast cancer, which is attributed mainly to targeting of MTDH and EZH2, however, the expression profile and therapeutic potential of miR-26a is still unclear. Here we demonstrate that miR-26a is down-regulated in breast cancer cells and clinical specimens and its modulation in breast cancer cells regulates cell proliferation, colony formation, migration and apoptosis. MCL-1, an anti-apoptotic member of the Bcl-2 family, as novel targets of miR-26a was found to be in reverse correlation with ectopic expression of miR-26a and knockdown of MCL-1 phenocopied the effect of miR-26a in breast cancer cell lines. It was further explored that miR-26a increased sensitivity of breast cancer cells to paclitaxel in which MCL-1 was involved. Thus, miR-26a impacts on cell proliferation and migration of breast cancer by regulating several carcinogenesis-related processes, including a novel mechanism involving the targeting of MCL-1.