miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer.
miR-148a-3p represses proliferation and EMT by establishing regulatory circuits between ERBB3/AKT2/c-myc and DNMT1 in bladder cancer.
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miR-148a-3p 通过在膀胱癌中建立 ERBB3/AKT2/c-myc 和 DNMT1 之间的调节回路来抑制增殖和 EMT。
DOI：
10.1038/cddis.2016.373
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发表时间：
2016-12-01
影响因子：
9
通讯作者：
Xie L
中科院分区：
文献类型：
--
作者：
Wang X;Liang Z;Xu X;Li J;Zhu Y;Meng S;Li S;Wang S;Xie B;Ji A;Liu B;Zheng X;Xie L
miR-148 a-3 p下调已成为肿瘤进展的关键因素，但miR-148 a-3 p表达模式及其在膀胱癌中的功能的潜在机制仍有待阐明。在这里，我们说明miR-148 a-3 p在膀胱癌中经常下调，其表达可能受DNA甲基化调控。DNA甲基转移酶1（DNMT 1）和miR-148 a-3 p在膀胱癌中的正反馈回路中发挥作用。miR-148 a-3 p过表达在膀胱癌细胞中起肿瘤抑制作用。miR-148 a-3 p通过调控ERBB 3/AKT 2/c-myc和ERBB 3/AKT 2/Snail信号通路抑制膀胱癌细胞增殖和上皮-间质转化（EMT）。ERBB 3、DNMT 1和AKT 2是miR-148 a-3 p的下游靶基因。此外，miR-148 a-3 p/ERBB 3/AKT 2/c-myc信号轴在膀胱癌的调节中建立了正反馈回路。总之，我们的研究证明了涉及miR-148 a-3 p/ERBB 3/AKT 2/c-myc和DNMT 1的控制膀胱癌进展的新调控回路，这可能有助于开发更有效的膀胱癌治疗方法。
miR-148a-3p downregulation has emerged as a critical factor in cancer progression yet, the underlying mechanisms of miR-148a-3p expression pattern and its function in bladder cancer remains to be elucidated. Here, we illustrate that miR-148a-3p is frequently downregulated in bladder cancer and that its expression may be regulated by DNA methylation. DNA methyltransferase 1 (DNMT1) and miR-148a-3p function in a positive feedback loop in bladder cancer. miR-148a-3p overexpression functions as a tumor suppressor in bladder cancer cells. miR-148a-3p inhibits bladder cancer cell proliferation and epithelial–mesenchymal transition (EMT) by regulating ERBB3/AKT2/c-myc and ERBB3/AKT2/Snail signaling. ERBB3, DNMT1 and AKT2 are downstream miR-148a-3p target genes. Furthermore, the miR-148a-3p/ERBB3/AKT2/c-myc signaling axis establishes a positive feedback loop in the regulation of bladder cancer. Taken together, our study demonstrates novel regulatory circuits involving miR-148a-3p/ERBB3/AKT2/c-myc and DNMT1 that controls bladder cancer progression, which may be useful in the development of more effective therapies against bladder cancer.