An oncogenic role of miR-592 in tumorigenesis of human colorectal cancer by targeting Forkhead Box O3A (FoxO3A)
An oncogenic role of miR-592 in tumorigenesis of human colorectal cancer by targeting Forkhead Box O3A (FoxO3A)
复制标题
miR-592 通过靶向 Forkhead Box O3A (FoxO3A) 在人结直肠癌肿瘤发生中的致癌作用
DOI：
10.1080/14728222.2016.1181753
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发表时间：
2016-01-01
影响因子：
5.8
通讯作者：
Yang, Yinxue
中科院分区：
文献类型：
--
作者：
Fu, Qi;Du, Yong;Yang, Yinxue
摘要目的：一种功能性下调肿瘤抑制因子表达的微小RNA（miRNA）可被定义为oncomir。在这里，我们询问miR-592在结直肠癌（CRC）中的生物学意义。研究设计和方法：通过qRT-PCR检测miR-592在结直肠癌组织和细胞系中的表达，并通过免疫组化染色检测其靶基因的表达。通过体外细胞增殖、迁移和克隆形成来评估miR-592的致癌作用，而通过体内抑制CRC细胞中的内源性miR-592来评估致瘤性。结果如下：与匹配的相邻非肿瘤组织和正常结肠细胞相比，在CRC组织和细胞系中观察到miR-592的显著上调。重要的是，叉头盒O3 A（FoxO 3A）被鉴定为miR-592的新靶点。miR-592抑制剂在CRC细胞中表现出显著的迁移、增殖和克隆形成减少。相对于对照细胞，这些细胞在SCID小鼠中也显示出降低的致瘤性。结论：miR-592可能通过靶向FoxO 3A促进结直肠癌的进展和转移。miR-592可能是治疗结直肠癌的新靶点，并且miR-592可以抑制结直肠癌细胞的增殖和转移。
ABSTRACT Objective: A microRNA (miRNA) that functionally downregulates the expression of tumor suppressors can be defined as an oncomir. Here, we interrogate the biological significance of miR-592 in colorectal cancer (CRC). Research design and methods: The expression of miR-592 in CRC tissues and cell lines was ascertained by qRT-PCR assay, and the expression of its target gene was determined by immunohistochemistry staining. The oncogenic role of miR-592 was assessed in terms of cell proliferation, migration, and clonogenicity in vitro, whereas the tumorigenicity was assessed by inhibiting endogenous miR-592 in CRC cells in vivo. Results: A striking upregulation of miR-592 was observed in CRC tissues and cell lines compared to the matched adjacent non-tumor tissues and normal colon cells. Importantly, Forkhead Box O3A (FoxO3A) was identified as a novel target of miR-592. miR-592 inhibitor exhibited a significant reduction of migration, proliferation, and clonogenicity in CRC cells. These cells also displayed a decreased tumorigenicity in SCID mice relative to the control cells. Conclusion: These data suggest that miR-592 may promote the progression and metastasis, in part, by targeting FoxO3A in CRC. miR-592 may be a novel target for CRC treatment and antagomir-592 may inhibit the proliferation and metastasis of CRC cells.