miR-942-5p Inhibits Proliferation, Metastasis, and Epithelial-Mesenchymal Transition in Colorectal Cancer by Targeting CCBE1.

miR-942-5p Inhibits Proliferation, Metastasis, and Epithelial-Mesenchymal Transition in Colorectal Cancer by Targeting CCBE1.
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miR-942-5p 通过靶向 CCBE1 抑制结直肠癌的增殖、转移和上皮间质转化

DOI:
10.1155/2021/9951405
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发表时间:
2021
影响因子:
--
通讯作者:
Tao M
Tao M
中科院分区:
生物学3区
文献类型:
--
作者:
Zhou L;Chen Q;Wu J;Yang J;Yin H;Tian J;Gong L;Kong D;Tao M

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虽然结直肠癌(CRC)是常见的,但关于其分子发病机制的信息很少。研究表明,miRNAs在结直肠癌的发生、发展中起着关键作用。有必要进一步研究miRNA在CRC中的生物学功能。特别地,已经报道了miR-942- 5 p表现出肿瘤抑制特性。因此,我们分析了miR-942- 5 p在CRC中的功能意义及其潜在的分子机制。我们发现miR-942- 5 p在结直肠癌组织和细胞中表达下调。Cell Counting Kit-8、EdU和集落形成测定显示,通过模拟物过表达miR-942- 5 p抑制CRC细胞的增殖。使用miR-942- 5 p抑制剂有效地增强了CRC细胞的增殖潜力。此外,体内异种移植实验证实了这些结果。miR-942- 5 p表达增加抑制CRC细胞系的侵袭、迁移和上皮-间质转化,而miR-942- 5 p表达降低则具有相反的作用。CCBE 1是一种淋巴管生成分泌分子,被确定为miR-942- 5 p的下游靶点,其表达与CRC细胞中miR-942- 5 p的表达呈负相关。此外,miR-942- 5 p抑制剂与si-CCBE 1共转染CRC细胞逆转了miR-942- 5 p过表达诱导的效应。总之,我们证实了miR-942- 5 p通过靶向CCBE 1在CRC中发挥致癌作用,并将miR-942- 5 p鉴定为CRC诊断和治疗的潜在临床生物标志物。
Although colorectal cancer (CRC) is common, there is a paucity of information regarding its molecular pathogenesis. Studies have shown that miRNAs play pivotal roles in the development and progression of CRC. There is a need to further investigate the biological functions of miRNAs in CRC. In particular, it has been reported that miR-942-5p exhibits tumor-suppressive properties. Thus, we analyzed the functional significance of miR-942-5p in CRC and the underlying molecular mechanisms. We found that miR-942-5p was downregulated in CRC tissues and cells. Cell Counting Kit-8, EdU, and colony formation assays revealed that the overexpression of miR-942-5p by mimics inhibited the proliferation of CRC cells. Use of the miR-942-5p inhibitor effectively enhanced the proliferative potential of CRC cells. Further, in vivo xenograft experiments confirmed these results. Increased expression of miR-942-5p suppressed the invasion, migration, and epithelial-mesenchymal transition of CRC cell lines, while decreased miR-942-5p expression had the opposite effect. CCBE1, a secretory molecule for lymphangiogenesis, was established as a downstream target of miR-942-5p, and its expression was inversely correlated with the expression of miR-942-5p in CRC cells. Additionally, cotransfection of the miR-942-5p inhibitor with si-CCBE1 into CRC cells reversed the effects induced by miR-942-5p overexpression. In conclusion, we confirmed that miR-942-5p exerts oncogenic actions in CRC by targeting CCBE1 and identified miR-942-5p as a potential clinical biomarker for CRC diagnosis and therapy.
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