A miR-124/ITGA3 axis contributes to colorectal cancer metastasis by regulating anoikis susceptibility
A miR-124/ITGA3 axis contributes to colorectal cancer metastasis by regulating anoikis susceptibility
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miR-124/ITGA3轴通过调节失巢凋亡易感性促进结直肠癌转移
DOI：
10.1016/j.bbrc.2018.05.062
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Sun JY
中科院分区：
文献类型：
--
作者：
Sa KD;Zhang x;Li XF;Gu ZP;Yang AG;Zhang R;Li JP;Sun JY
转移是结直肠癌患者死亡的主要原因。失巢凋亡抗性增强了癌细胞在体循环期间的存活，从而促进了远处器官中的继发性肿瘤形成。miR-124是一种多效的肿瘤抑制性小非编码分子。然而，其在调节癌细胞失巢凋亡中的作用和机制尚不清楚。在此，我们发现miR-124的过表达在体外和体内促进CRC细胞的失巢凋亡。计算机模拟分析和实验证据支持ITGA 3是miR-124的真正靶标。此外，我们确定ITGA 3在CRC细胞中失巢凋亡敏感性的调节中起关键作用。最后，我们对TCGA数据集的分析表明，高水平的ITGA 3与CRC患者的不良预后密切相关。总之，我们建立了miR-124和失巢凋亡易感性之间的功能联系，并提供了miR-124/ITGA 3轴可能是治疗转移性CRC的潜在靶点。
Metastasis is the major cause for the death of patients with colorectal cancer (CRC). Anoikis resistance enhances the survival of cancer cells during systemic circulation, thereby facilitating secondary tumor formation in distant organs. miR-124 is a pleiotropically tumor suppressive small non-coding molecule..However, its role and mechanism in the regulation of cancer cell anoikis are still unknown. Here, we.found that overexpression of miR-124 promotes anoikis of CRC cells in vitro and in vivo. In silico analysis.and the experimental evidence supported that ITGA3 is a bona fide target of miR-124. Moreover, we.identifies that ITGA3 plays a critical role in the regulation of anoikis sensitivity in CRC cells. Finally, our.analysis in TCGA datasets demonstrates that high levels of ITGA3 are closely associated with poor.prognosis in CRC patients. Collectively, we establish a functional link between miR-124 and anoikis.susceptibility and provide that a miR-124/ITGA3 axis could be a potential target for the treatment of.metastatic CRC.