Song Qiong, Song Jiangqiang, Wang Qimin, Ma Yanling, Sun Nai, Ma Jieyu, Chen Qiu, Xia Guishan, Huo Yanping, Yang Longqiu, Li Baolin
Department of Anesthesiology, Zhengzhou Central Hospital Affiliated to Zhengzhou University, 195 Tongbai Road, Zhengzhou, Henan, 450007, China.
Department of Galactophore, Zhengzhou Central Hospital Affiliated to Zhengzhou University, 195 Tongbai Road, Zhengzhou, Henan, 450007, China.
Cancer Med. 2016 Feb;5(2):315-24. doi: 10.1002/cam4.567. Epub 2015 Dec 13.
Fast growth and hardly any apoptosis are important characteristics of breast cancer, which assure the spread via invasion and metastasis of breast cancer cells. Inhibition of fast proliferation and induction of apoptosis are critical way to cure this cancer. microRNAs (miRNAs) had been increasingly reported to be the critical regulator of tumorigenesis. In our study, we found that increasing copy number of miR-548d-2-3p is critically involved poor prognosis. We overexpressed miR-548d-3p in MDA-MB-231cells and found that the proliferation was promoted significantly, whereas the inhibition of miR-548d-3p repressed the proliferation of MDA-MB-231 cells and also induced the increase in apoptosis. Additionally, we found that miR-548d-3p downregulated the expression of TP53BP2 by directly targeting the 3'UTR. We also found that knockdown of TP53BP2 significantly resorted the proliferation and apoptosis regulated by miR-548d-3p inhibitor. Our study showed that miR-548d-3p/TP53BP2 pathway is critically involved in the proliferation and apoptosis of breast cancer cells and may be new therapeutic target of breast cancer cells.
快速生长且几乎没有细胞凋亡是乳腺癌的重要特征,这确保了乳腺癌细胞通过侵袭和转移进行扩散。抑制快速增殖和诱导细胞凋亡是治愈这种癌症的关键途径。越来越多的研究报道,微小RNA(miRNA)是肿瘤发生的关键调节因子。在我们的研究中,我们发现miR-548d-2-3p拷贝数增加与不良预后密切相关。我们在MDA-MB-231细胞中过表达miR-548d-3p,发现细胞增殖显著促进,而抑制miR-548d-3p则抑制MDA-MB-231细胞的增殖,并诱导细胞凋亡增加。此外,我们发现miR-548d-3p通过直接靶向3'UTR下调TP53BP2的表达。我们还发现,敲低TP53BP2可显著恢复miR-548d-3p抑制剂对细胞增殖和凋亡的调节作用。我们的研究表明,miR-548d-3p/TP53BP2通路与乳腺癌细胞的增殖和凋亡密切相关,可能是乳腺癌细胞新的治疗靶点。