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Let-7i-3p通过下调CCND1抑制结肠癌细胞的细胞周期、增殖、侵袭和迁移。

Let-7i-3p inhibits the cell cycle, proliferation, invasion, and migration of colorectal cancer cells via downregulating CCND1.

作者信息

Tu Fei, Li Mengfan, Chen Yinyu, Chu Huiru, Wang Shujie, Hai Lun, Xie Ting, Geng Fangfang, Zhao Tiesuo, Wang Qingzhi, Feng Zhiwei

机构信息

Department of Anatomy, Histology & Embryology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, China.

Institute of Precision Medicine, Xinxiang Medical University, Xinxiang, China.

出版信息

Open Med (Wars). 2022 Jun 7;17(1):1019-1030. doi: 10.1515/med-2022-0499. eCollection 2022.

Abstract

Dysregulated microRNAs are closely related to the malignant progression of colorectal cancer (CRC). Although abnormal let-7i-3p expression has been reported in various human cancers, its biological role and potential mechanism in CRC remain unclear. Therefore, the purpose of this study was to investigate the expression and regulation of let-7i-3p in CRC. Here, we demonstrated that let-7i-3p expression was significantly downregulated in three CRC cell lines while CyclinD1 (CCND1) was upregulated compared with the normal colon epithelial FHC cells. Moreover, bioinformatics and luciferase reporter assays revealed that CCND1 was a direct functional target of let-7i-3p. In addition, let-7i-3p overexpression or CCND1 silencing inhibited cell cycle, proliferation, invasion, and migration and diminished the activation of p-ERK in HCT116 cells. However, exogenously expressing CCND1 alleviated these effects. Taken together, our findings may provide new insight into the pathogenesis of CRC and let-7i-3p/CCND1 might function as new therapeutic targets for CRC.

摘要

失调的微小RNA与结直肠癌(CRC)的恶性进展密切相关。尽管在多种人类癌症中已报道let-7i-3p表达异常,但其在CRC中的生物学作用和潜在机制仍不清楚。因此,本研究的目的是探讨let-7i-3p在CRC中的表达及调控。在此,我们证明与正常结肠上皮FHC细胞相比,三种CRC细胞系中let-7i-3p表达显著下调,而细胞周期蛋白D1(CCND1)上调。此外,生物信息学和荧光素酶报告基因检测显示CCND1是let-7i-3p的直接功能靶点。另外,let-7i-3p过表达或CCND1沉默抑制了HCT116细胞的细胞周期、增殖、侵袭和迁移,并降低了p-ERK的激活。然而,外源性表达CCND1可减轻这些影响。综上所述,我们的研究结果可能为CRC的发病机制提供新的见解,且let-7i-3p/CCND1可能作为CRC的新治疗靶点发挥作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ad25/9175015/cc5ef1ce763c/j_med-2022-0499-fig001.jpg

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