Zhou Ci-Xiang, Wang Chen-Long, Yu An-Lu, Wang Qiu-Yu, Zhan Meng-Na, Tang Jun, Gong Xiu-Feng, Yin Qian-Qian, He Ming, He Jian-Rong, Chen Guo-Qiang, Zhao Qian
Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of National Ministry of Education, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai 200025, China.
Institute of Health Sciences, SJTU-SM & Shanghai Institutes for Biological Sciences (SIBS), Chinese Academy of Sciences (CAS), Shanghai 200025, China.
Oncotarget. 2016 Jan 12;7(2):1288-99. doi: 10.18632/oncotarget.6339.
MicroRNAs have been integrated into tumorigenic programs as either oncogenes or tumor suppressor genes. The miR-630 was reported to be deregulated and involved in tumor progression of several human malignancies. However, its expression regulation shows diversity in different kinds of cancers and its potential roles remain greatly elusive. Herein, we demonstrate that miR-630 is significantly suppressed in human breast cancer specimens, as well as in various breast cancer cell lines. In aggressive MDA-MB-231-luc and BT549 breast cancer cells, ectopic expression of miR-630 strongly inhibits cell motility and invasive capacity in vitro. Moreover, lentivirus delivered miR-630 bestows MDA-MB-231-luc cells with the ability to suppress cell colony formation in vitro and pulmonary metastasis in vivo. Further studies identify metadherin (MTDH) as a direct target gene of miR-630. Functional studies shows that MTDH contributes to miR-630-endowed effects including cell migration and invasion as well as colony formation in vitro. Taken together, these findings highlight an important role for miR-630 in the regulation of metastatic potential of breast cancer and suggest a potential application of miR-630 in breast cancer treatment.
微小RNA已作为癌基因或肿瘤抑制基因被整合到肿瘤发生程序中。据报道,miR-630失调并参与了多种人类恶性肿瘤的肿瘤进展。然而,其表达调控在不同类型的癌症中表现出多样性,其潜在作用仍知之甚少。在此,我们证明miR-630在人类乳腺癌标本以及各种乳腺癌细胞系中均被显著抑制。在侵袭性MDA-MB-231-luc和BT549乳腺癌细胞中,miR-630的异位表达在体外强烈抑制细胞运动性和侵袭能力。此外,慢病毒递送的miR-630赋予MDA-MB-231-luc细胞在体外抑制细胞集落形成和在体内抑制肺转移的能力。进一步的研究确定黏附分子(MTDH)是miR-630的直接靶基因。功能研究表明,MTDH促成了miR-630赋予的效应,包括细胞迁移、侵袭以及体外集落形成。综上所述,这些发现突出了miR-630在调节乳腺癌转移潜能中的重要作用,并提示miR-630在乳腺癌治疗中的潜在应用。