The members of the integrin αv (ITGAV) family are widely expressed on many types of tumors and have been reported to be involved into angiogenesis, tumor metastases, and multicellular radioresistance. Osteosarcoma (OS) is the most common primary malignant bone tumor and the role of ITGAV in OS needs to be further elucidated. MicroRNAs are aberrantly expressed in a variety of cancers. Thus, the authors collected OS tissues (n = 15) and corresponding paracancerous tissues (n = 15) and found that the expression of miR-548c-3p was significantly downregulated in OS tissues and cell lines 143B, SaoS2, and HOS when compared to the corresponding paracancerous tissues and human osteoblast cell line hFOB (OB3), respectively. In addition, the authors identified that miR-548c-3p could directly target the 3'-untranslated region of ITGAV, and miR-548c-3p overexpression inhibits the mRNA and protein levels of ITGAV, which were confirmed by the luciferase reporter assays. Interestingly, they also uncovered that miR-548c-3p overexpression or knockdown of ITGAV remarkably suppressed cell vitality and promoted apoptosis and G2/M cell cycle arrest, leading to abrogating the ability of colony formation. The results indicated that the miR-548c-3p, similar to the target agents against integrin αv in clinical trials, could negatively regulate the ITGAV and be a promising tumor therapeutic target.
As a member of the p160 steroid receptor coactivator (SRC) family, nuclear receptor coactivator 2 (NCOA2) is known to play essential roles in many physiological and pathological processes, including development, endocrine regulation, and tumorigenesis. However, the biological function of NCOA2 in breast cancer is not fully understood. We found that the copy number of the NCOA2 gene was frequently amplified in four breast cancers datasets, varying from 6 to 10%, and the mRNA levels of NCOA2 were also upregulated in 11% of the sequenced cases/patients (TCGA provisional dataset). Next, we confirmed that NCOA2 silencing significantly suppressed cell proliferation in different breast cancer cell lines, by inducing cell cycle arrest and apoptosis. Mechanistically, whole-transcriptome sequencing (RNA-Seq) analysis showed that NCOA2 depletion leads to downregulation of the MAPK/ERK signaling cascade, possibly via downregulating NCOA2's downstream target RASEF. In conclusion, our results suggest NCOA2 as a potential target of therapeutics against breast cancer.
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