MicroRNA-126 inhibits colon cancer cell proliferation and invasion by targeting the chemokine (C-X-C motif) receptor 4 and Ras homolog gene family, member A, signaling pathway.
MicroRNA-126 inhibits colon cancer cell proliferation and invasion by targeting the chemokine (C-X-C motif) receptor 4 and Ras homolog gene family, member A, signaling pathway.
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MicroRNA-126通过靶向趋化因子（C-X-C基序）受体4和Ras同源基因家族成员A信号通路抑制结肠癌细胞增殖和侵袭
DOI：
10.18632/oncotarget.11176
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发表时间：
2016-09-13
期刊：
影响因子：
--
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Yuan W;Guo YQ;Li XY;Deng MZ;Shen ZH;Bo CB;Dai YF;Huang MY;Yang ZY;Quan YS;Tian L;Wang X
MicroRNA-126 （miR-126）抑制结肠癌细胞的迁移、增殖和侵袭。然而，miR-126在结肠癌中的潜在机制尚未完全阐明。在本研究中，体内实验发现miR-126抑制结肠癌的生长和转移。此外，miR-126在人结肠癌组织中下调，其表达与患者TNM分期和转移呈负相关。miR-126水平低可识别预后差的患者。我们发现miR-126的表达在体外和体内与趋化因子（C-X-C motif）受体4 （CXCR4）和Ras同源基因家族信号通路组分成员A （RhoA）的表达水平呈负相关。此外，我们在体外验证了miR-126负调控CXCR4和RhoA信号。此外，无论是在miR-126过表达还是miR-126沉默的结肠癌细胞中，CXCR4的恢复都可以显著逆转增殖和侵袭，并消除miR-126对RhoA信号通路的影响。综上所述，这些结果表明miR-126在结肠癌中通过CXCR4失活RhoA信号作为肿瘤抑制因子。miR-126可能作为监测和治疗结肠癌的预后标志物。
MicroRNA-126 (miR-126) suppresses the migration, proliferation and invasion of colon cancer cells. However, the underlying mechanisms of miR-126 in colon cancer have not been fully elucidated. In this study, in vivo experiments revealed that miR-126 inhibits colon cancer growth and metastasis. Furthermore, miR-126 was down-regulated in human colon cancer tissue, and its expression was inversely correlated with TNM stage and metastasis of patients. Low level of miR-126 identified patients with poor prognosis. And we found that miR-126 expression was negatively correlated with the expression levels of chemokine (C-X-C motif) receptor 4 (CXCR4) and components of signaling pathway of Ras homolog gene family, member A (RhoA) in vitro and in vivo. Moreover, we verified that miR-126 negatively regulated CXCR4 and RhoA signaling in vitro. In addition, either in miR-126-overexpressing or in miR- 126-silenced colon cancer cells, the restoration of CXCR4 could significantly reverse the proliferation and invasion, as well as abolish the effects of miR-126 on RhoA signaling pathway. Collectively, these results demonstrated that miR-126 acts as a tumor suppressor by inactivating RhoA signaling via CXCR4 in colon cancer. And miR-126 may serve as a prognostic marker for monitoring and treating colon cancer.