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microRNA-4429-5p suppresses the malignant development of colon cancer by targeting matrix metalloproteinase 16
In Vitro Cellular & Developmental Biology - Animal ( IF 2.1 ) Pub Date : 2021-08-26 , DOI: 10.1007/s11626-021-00603-4
Wei Li 1 , Zhe Song 1 , Nan Jia 1 , Cui Zhang 1 , Weina Gao 2 , Liang Wang 1
Affiliation  

Colon cancer has been recognized as the major reason for global cancer-associated mortality. microRNA (miRNA, miR)-4429-5p has been documented to act as a tumor-suppressive miRNA in some cancers, but its effect on colon cancer remains elusive. In this study, the biological effects of miR-4429-5p were investigated both in vitro by MTT, 5-ethynyl-2′-deoxyuridine (EdU), wound healing, and transwell assays and in vivo by a xenograft mice model. Western blot, quantitative reverse transcription-polymerase chain reaction (qRT-PCR), and dual-luciferase assay were used to identify the binding of miR-4429-5p on matrix metalloproteinase 16 (MMP16) 3′-UTR. Our results suggested that overexpression of miR-4429-5p hindered colon cancer cell proliferation, migration, and invasion, whereas knockdown of miR-4429-5p exhibited the opposite effect in colon cancer cells. Mechanistically, miR-4429-5p directly bound to the 3′-UTR of MMP16 and led to inhibition of MMP16 protein. Overexpression of miR-4429-5p inhibited colon tumor growth by targeting MMP16. Taken together, our study revealed that miR-4429-5p prevented colon cancer progression through targeting MMP16, indicating miR-4429-5p as a promising target for treatment improvement for colon cancer.



中文翻译:

microRNA-4429-5p 通过靶向基质金属蛋白酶 16 抑制结肠癌的恶性发展

结肠癌已被公认为全球癌症相关死亡率的主要原因。microRNA (miRNA, miR)-4429-5p 已被证明在某些癌症中充当肿瘤抑制 miRNA,但其对结肠癌的影响仍然难以捉摸。在这项研究中,miR-4429-5p 的生物学效应在体外通过 MTT、5-乙炔基-2'-脱氧尿苷 (EdU)、伤口愈合和 transwell 试验以及在体内通过异种移植小鼠模型进行了研究。使用蛋白质印迹、定量逆转录聚合酶链反应 (qRT-PCR) 和双荧光素酶测定来鉴定 miR-4429-5p 与基质金属蛋白酶 16 (MMP16) 3'-UTR 的结合。我们的研究结果表明,miR-4429-5p 的过表达阻碍了结肠癌细胞的增殖、迁移和侵袭,而 miR-4429-5p 的敲低在结肠癌细胞中表现出相反的效果。机制上,miR-4429-5p 直接与 MMP16 的 3'-UTR 结合并导致 MMP16 蛋白的抑制。miR-4429-5p 的过表达通过靶向 MMP16 抑制结肠肿瘤的生长。总之,我们的研究表明,miR-4429-5p 通过靶向 MMP16 预防结肠癌进展,表明 miR-4429-5p 是改善结肠癌治疗的有希望的靶点。

更新日期:2021-08-27
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