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miR-942-5p 通过靶向 CCBE1 抑制结直肠癌细胞的增殖、转移和上皮间质转化。

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

机构信息

Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, China.

Department of Oncology, Jingjiang People's Hospital, Jingjiang, Jiangsu 214504, China.

出版信息

Biomed Res Int. 2021 Apr 28;2021:9951405. doi: 10.1155/2021/9951405. eCollection 2021.

Abstract

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, 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.

摘要

尽管结直肠癌(CRC)很常见,但关于其分子发病机制的信息却很少。研究表明,miRNAs 在 CRC 的发生和发展中起着关键作用。需要进一步研究 miRNAs 在 CRC 中的生物学功能。特别是,据报道 miR-942-5p 具有肿瘤抑制特性。因此,我们分析了 miR-942-5p 在 CRC 中的功能意义及其潜在的分子机制。我们发现 miR-942-5p 在 CRC 组织和细胞中下调。细胞计数试剂盒-8、EdU 和集落形成实验表明,miR-942-5p 模拟物的过表达抑制了 CRC 细胞的增殖。使用 miR-942-5p 抑制剂有效地增强了 CRC 细胞的增殖潜能。此外,异种移植实验证实了这些结果。miR-942-5p 的表达增加抑制了 CRC 细胞系的侵袭、迁移和上皮间质转化,而 miR-942-5p 表达的减少则产生相反的效果。CCBE1 是淋巴管生成的分泌分子,被确定为 miR-942-5p 的下游靶标,其在 CRC 细胞中的表达与 miR-942-5p 的表达呈负相关。此外,将 miR-942-5p 抑制剂与 si-CCBE1 共转染到 CRC 细胞中,逆转了 miR-942-5p 过表达引起的作用。总之,我们证实 miR-942-5p 通过靶向 CCBE1 在 CRC 中发挥致癌作用,并将 miR-942-5p 鉴定为 CRC 诊断和治疗的潜在临床生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9358/8102100/2f8a3d1d655c/BMRI2021-9951405.001.jpg

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