Han Sanghak, Zou Hua, Lee Jin-Won, Han Jeonghee, Kim Heung Cheol, Cheol Jeong Jin, Kim Lee-Su, Kim Haesung
Department of Pathology, Chuncheon Sacred Heart Hospital, College of Medicine, Hallym University, Chuncheon 24253, Gangwon-Do, South Korea.
Cancer Center, Daping Hospital and Research Institute of Surgery, Third Military Medical University, Chongqing 400042, China.
J Cancer. 2019 Jan 1;10(2):441-448. doi: 10.7150/jca.30041. eCollection 2019.
Recent studies show that dysregulated miRNAs play an important role in breast cancer initiation and progression. Here, we identified upregulated expression of miR-1307-3p in breast cancer tissues and that increased level of miR-1307-3p was closely correlated with lower survival rate in breast cancer patients. Consistent with clinical data, our data show that expression level of miR-1307-3p was significantly increased in breast cancer cell lines compared to human mammary epithelial cell line MCF10A. Overexpression of miR-1307-3p in MCF10A stimulated cell proliferation and caused their growth in soft agar and tumor formation in nude mice. In contrast, inhibition of miR-1307-3p suppressed breast cancer cell proliferation and their growth in soft agar and inhibited tumor formation in nude mice. Further, we identified that miR-1307-3p plays its oncogenic role through targeting SET and MYND domain-containing 4 (SMYD4) expression in breast cancer. Taken together, our findings suggest that miR-1307-3p is a oncogenic miRNA that significantly contributes to breast cancer development and progression, and inhibition of miR-1307-3p may be a novel strategy for inhibits breast cancer initiation and progression.
近期研究表明,失调的微小RNA(miRNA)在乳腺癌的发生和发展中起重要作用。在此,我们发现乳腺癌组织中miR-1307-3p表达上调,且miR-1307-3p水平升高与乳腺癌患者较低的生存率密切相关。与临床数据一致,我们的数据显示,与人类乳腺上皮细胞系MCF10A相比,乳腺癌细胞系中miR-1307-3p的表达水平显著升高。在MCF10A中过表达miR-1307-3p可刺激细胞增殖,并使其在软琼脂中生长以及在裸鼠中形成肿瘤。相反,抑制miR-1307-3p可抑制乳腺癌细胞增殖及其在软琼脂中的生长,并抑制裸鼠中的肿瘤形成。此外,我们发现miR-1307-3p通过靶向乳腺癌中含SET和MYND结构域的4(SMYD4)表达发挥其致癌作用。综上所述,我们的研究结果表明,miR-1307-3p是一种致癌性miRNA,对乳腺癌的发生和发展有显著贡献,抑制miR-1307-3p可能是抑制乳腺癌起始和进展的一种新策略。