miR-3120-5p promotes colon cancer stem cell stemness and invasiveness through targeting Axin2.
miR-3120-5p promotes colon cancer stem cell stemness and invasiveness through targeting Axin2.
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miR-3120-5p通过靶向Axin2促进结肠癌干细胞的干细胞稳定性和侵袭性
DOI：
10.1016/j.bbrc.2018.01.021
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发表时间：
2018-02-05
影响因子：
3.1
通讯作者：
Feng, Li
中科院分区：
文献类型：
--
作者：
Hongdan, Li;Feng, Li
众所周知，结肠癌的干性和侵袭性是肿瘤复发和转移的主要原因。本研究以结肠癌细胞株HCT-116和SW-480为研究对象，探讨miR-3120- 5 p对结肠癌细胞增殖、侵袭和转移的影响。我们发现两种细胞系中的CD 133+和Lgr 5+干细胞群体高度表达miR-3120- 5 p，并且将miR-3120- 5 p引入两种细胞系中增加了癌症干细胞群体，如通过流式细胞术、qRT-PCR和球体形成测定所测量的。Transwell法、明胶酶谱法和Western blot法进一步揭示miR-3120- 5 p促进结肠癌细胞的侵袭能力。通过靶点预测算法TargetScan，发现Axin 2是miR-3120- 5 p的潜在靶点，荧光素酶报告基因实验表明miR-3120- 5 p可降低Axin 2的表达。针对Axin 2的SiRNA转染结肠癌细胞可促进结肠癌细胞的干性和侵袭性。此外，Axin 2过表达部分逆转了miR-3120- 5 p在结肠癌细胞中引起的干性和侵袭性的促进。总之，所有结果都表明miR-3120- 5 p通过直接靶向Axin 2促进结肠癌细胞的干性和侵袭性。这表明miR-3120- 5 p在结肠癌的治疗策略中起着重要作用。
It is well known that colon cancer stemness and invasiveness are the main reasons for tumor recurrence and metastasis. MicroRNAs dysregulation can disrupt the balance of cell signaling and growth processes, resulting in cancer proliferation, invasion and metastasis, chemoresistance and so on. In this study, we used colon cancer cell lines HCT-116 and SW-480 to investigate the effects of miR-3120-5p on stemness and invasiveness of colon cancer. We found that the population of CD133+and Lgr5+ stem cells in both cell lines expressed miR-3120-5p highly, and introducing miR-3120-5p into both cell lines increased the population of cancer stem cells, as measured by flow cytometry, qRT-PCR and sphere formation assays. Transwell assay, Gelatin zymography assay and Western blot assays further revealed that miR-3120-5p promotes colon cancer cells invasive ability. By the target prediction algorithm TargetScan, we found Axin2 is a potential target for miR-3120-5p, and luciferase reporter assay demonstrated that miR-3120-5p reduces Axin2 expression. Transfection of siRNA against Axin2 into colon cancer cells promoted the stemness and invasion of colon cancer cells. Furthermore, Axin2 overexpression partially reversed the promotion of stemness and invasiveness caused by miR-3120-5p in colon cancer cells. Together, all the results demonstrated miR-3120-5p promotes stemness and invasiveness of colon cancer cells through direct targeting of Axin2. They suggest that antago-miR-3120-5p plays important roles on treatment strategy for colon cancer.