microRNA-613 通过靶向 ATOH1 促进结肠癌细胞的增殖、侵袭和迁移。
MicroRNA-613 promotes colon cancer cell proliferation, invasion and migration by targeting ATOH1.
机构信息
Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu Changzhou, 213003, China; Jiangsu Engineering Research Center for Tumor Immunotherapy, The Third Affiliated Hospital of Soochow University, Jiangsu Changzhou, 213003, China.
Department of Radiation Oncology, The Third Affiliated Hospital of Soochow University, Jiangsu Changzhou, 213003, China.
出版信息
Biochem Biophys Res Commun. 2018 Oct 12;504(4):827-833. doi: 10.1016/j.bbrc.2018.09.054. Epub 2018 Sep 13.
The aim of the present study is to investigate the expression and function of miR-613 in colon cancer (CC) and illuminate the molecular mechanisms underlying miR-613-regulated CC progression. Our data demonstrated that miR-613 was upregulated in CC tissue samples (P = 0.009) and human CC cell lines (HCT-116 and Lovo; P = 0.001 and P = 0.003, respectively), which also promoted the proliferation, invasion and migration of CC cells (P < 0.05). The dual-luciferase reporter assay confirmed that Atonal homolog1 (ATOH1) was the target mRNA of miR-613. Rescue experiments showed that ATOH1 overexpression vector significantly reversed the stimulative effects of miR-613 mimic on the progression of HCT-116 and Lovo cells (P < 0.001). Positive ATOH1 expression in CC tissues was significantly associated with lower grade (χ = 3.592, P = 0.043), lower TNM stage (χ = 3.537, P = 0.048) and better overall survival (P=0.041). Jun N-terminal kinase 1 (JNK1) pathway and Mucin 2 (MUC2) were the potential downstream proteins of miR-613/ATOH1. miR-613 is an oncogene in CC and promotes the proliferation, invasion and migration of CC cells by targeting ATOH1 likely via activating JNK1 pathway and upregulating MUC2.
本研究旨在探究 miR-613 在结肠癌（CC）中的表达和功能，并阐明 miR-613 调控 CC 进展的分子机制。我们的数据表明，miR-613 在 CC 组织样本中上调（P=0.009）和人 CC 细胞系（HCT-116 和 Lovo；P=0.001 和 P=0.003）中上调，这也促进了 CC 细胞的增殖、侵袭和迁移（P<0.05）。双荧光素酶报告基因实验证实 Atonal homolog1（ATOH1）是 miR-613 的靶 mRNA。挽救实验表明，ATOH1 过表达载体显著逆转了 miR-613 模拟物对 HCT-116 和 Lovo 细胞进展的刺激作用（P<0.001）。CC 组织中 ATOH1 的阳性表达与较低的分级（χ²=3.592，P=0.043）、较低的 TNM 分期（χ²=3.537，P=0.048）和更好的总生存（P=0.041）显著相关。Jun N-terminal kinase 1（JNK1）通路和 Mucin 2（MUC2）是 miR-613/ATOH1 的潜在下游蛋白。miR-613 是 CC 的致癌基因，通过靶向 ATOH1 可能通过激活 JNK1 通路和上调 MUC2 促进 CC 细胞的增殖、侵袭和迁移。
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