miR-1307-3p Stimulates Breast Cancer Development and Progression by Targeting SMYD4

miR-1307-3p Stimulates Breast Cancer Development and Progression by Targeting SMYD4
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DOI:
10.7150/jca.30041
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发表时间:
2019-01-01
期刊:
影响因子:
3.9
通讯作者:
Kim, Haesung
Kim, Haesung
中科院分区:
医学3区
文献类型:
--
作者:
Han, Sanghak;Zou, Hua;Kim, Haesung

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最近的研究表明,失调的mirna在乳腺癌的发生和发展中起着重要作用。本研究中,我们发现miR-1307-3p在乳腺癌组织中表达上调,miR-1307-3p水平升高与乳腺癌患者生存率降低密切相关。与临床数据一致,我们的体外数据显示,miR-1307-3p在乳腺癌细胞系中的表达水平比人乳腺上皮细胞系MCF10A显著升高。MCF10A中过表达miR-1307-3p可刺激细胞增殖,使其在裸鼠软琼脂中生长并形成肿瘤。相反,抑制miR-1307-3p抑制乳腺癌细胞在软琼脂中的增殖和生长,抑制裸鼠的肿瘤形成。此外,我们发现miR-1307-3p通过靶向SET和MYND结构域4 (SMYD4)在乳腺癌中的表达来发挥其致癌作用。综上所述,我们的研究结果表明,miR-1307-3p是一种致癌miRNA,对乳腺癌的发生和进展有重要作用,抑制miR-1307-3p可能是抑制乳腺癌发生和进展的一种新策略。
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 in vitro 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.