MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells.
MicroRNA-99a inhibits tumor aggressive phenotypes through regulating HOXA1 in breast cancer cells.
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MicroRNA-99a 通过调节乳腺癌细胞中的 HOXA1 抑制肿瘤侵袭表型。
DOI：
10.18632/oncotarget.5355
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发表时间：
2015-10-20
期刊：
影响因子：
--
通讯作者：
Yang Q
中科院分区：
文献类型：
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作者：
Wang X;Li Y;Qi W;Zhang N;Sun M;Huo Q;Cai C;Lv S;Yang Q
microRNA（miRNAs）是肿瘤进展的关键调节因子。基于微阵列数据，我们鉴定了miR-99 a作为乳腺癌的潜在肿瘤抑制因子。相对于正常乳腺组织，miR-99 a的表达在乳腺癌组织中经常下调。miR-99 a表达降低与乳腺癌患者的淋巴结转移和总生存期缩短高度相关。功能获得和丧失研究表明，miR-99 a显著抑制乳腺癌细胞增殖、迁移和侵袭。综合生物信息学分析确定HOXA 1 mRNA是miR-99 a的直接功能靶点，并通过荧光素酶报告基因分析证实了这种调控作用。此外，我们首次发现HOXA 1表达在乳腺癌组织中升高。HOXA 1的敲低显著抑制乳腺癌细胞的增殖、迁移和侵袭，并且HOXA 1的恢复部分地挽救了miR-99 a在乳腺癌细胞中的抑制作用。总之，我们的数据表明，miR-99 a在乳腺癌的发展中起着肿瘤抑制作用，并可能作为乳腺癌治疗的潜在治疗靶点。
MicroRNAs (miRNAs) are key regulators of tumor progression. Based on microarray data, we identified miR-99a as a potential tumor suppressor in breast cancer. Expression of miR-99a is frequently down-regulated in breast cancer tissues relative to normal breast tissues. Reduced miR-99a expression was highly associated with lymph node metastasis and shorter overall survival of patients with breast cancer. Gain- and loss-of-function studies revealed that, miR-99a significantly inhibits breast cancer cell proliferation, migration, and invasion. An integrated bioinformatics analysis identified HOXA1 mRNA as the direct functional target of miR-99a, and this regulation was confirmed by luciferase reporter assay. Furthermore, we showed for the first time that HOXA1 expression is elevated in breast cancer tissues. Knockdown of HOXA1 significantly inhibited breast cancer cell proliferation, migration and invasion, and restoration of HOXA1 partially rescued the inhibitory effect of miR-99a in breast cancer cells. Collectively, our data indicate that miR-99a plays a tumor-suppressor role in the development of breast cancer, and could serve as a potential therapeutic target for breast cancer treatment.