MicroRNA-613 promotes colon cancer cell proliferation, invasion and migration by targeting ATOH1.
MicroRNA-613 promotes colon cancer cell proliferation, invasion and migration by targeting ATOH1.
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DOI：
10.1016/j.bbrc.2018.09.054
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发表时间：
2018-10
影响因子：
3.1
通讯作者：
Xuanxuan Yang;Luo-Ying Zhang;Xing Song;Wenting He;Dachuan Zhang;Qicheng Lu;Jun Wu;Changping Wu-Changpin
中科院分区：
文献类型：
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作者：
Xuanxuan Yang;Luo-Ying Zhang;Xing Song;Wenting He;Dachuan Zhang;Qicheng Lu;Jun Wu;Changping Wu-Changpin
本研究的目的是研究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组织样品（P= 0.009）和人CC细胞系（HCT-116和Lovo;分别为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检测证实Atonal homolog 1（ATOH 1）是miR-613的靶mRNA。拯救实验显示ATOH 1过表达载体可显著逆转miR-613模拟物对HCT-116和Lovo细胞的促增殖作用（P< 0.001）。ATOH 1阳性表达与肿瘤分级、TNM分期及总生存率相关（χ2= 3.592，P = 0.043、χ2= 3.537，P = 0.048、P=0.041）。Jun N-末端激酶1（JNK 1）通路和粘蛋白2（MUC 2）是miR-613/ATOH 1的潜在下游蛋白。miR-613是CC中的一种癌基因，可能通过激活JNK 1通路和上调MUC 2而靶向ATOH 1，从而促进CC细胞的增殖、侵袭和迁移。
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 andP= 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 (χ2= 3.592,P= 0.043), lower TNM stage (χ2= 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.