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微小RNA-1236-3p通过靶向双皮质素样激酶3抑制结肠癌细胞的增殖、侵袭和迁移,并阻碍上皮-间质转化。

MiR-1236-3p Inhibits the Proliferation, Invasion, and Migration of Colon Cancer Cells and Hinders Epithelial-Mesenchymal Transition by Targeting DCLK3.

作者信息

Zhao Yibin, Zhou Hongyi, Shen Jie, Yang Shaohui, Deng Ke, Li Qi, Cui Wei

机构信息

Department of Colorectal Surgery, Ningbo Medical Center Lihuili Hospital, Ningbo City, China.

出版信息

Front Oncol. 2021 Sep 3;11:688882. doi: 10.3389/fonc.2021.688882. eCollection 2021.

Abstract

BACKGROUND

Dysregulated microRNAs (miRNAs) are common in human cancer and are involved in the proliferation, promotion, and metastasis of tumor cells. Therefore, this study aimed to evaluate the expression and biological function of miR-1236-3p in colon cancer.

METHODS

This study screened the miRNA in normal and colon cancer tissues through array analysis. In addition, quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) analysis was performed to validate the expression of miR-1236-3p in normal and tumor tissues from colon cancer patients and cancer cell lines. Online predicting algorithms and luciferase reporter assays were also employed to confirm Doublecortin Like Kinase 3 (DCLK3) was the target for miR-1236-3p. Moreover, the impact of miR-1236-3p on the progression of colon cancer was evaluated and . Western blotting and qRT-PCR were also performed to investigate the interactions between miR-1236-3p and DCLK3.

RESULTS

MiR-1236-3p was significantly downregulated in colon cancer tissues and its expression was associated with the TNM stage and metastasis of colon. In addition, the and experiments showed that miR-1236-3p significantly promoted cancer cell apoptosis and inhibited the proliferation, invasion, and migration of cancer cells. The results also showed that miR-1236-3p hindered Epithelial-mesenchymal Transition (EMT) by targeting DCLK3. Moreover, the expression of DCLK3 mediated the effects of miR-1236-3p on the progression of cancer.

CONCLUSIONS

MiR-1236-3p functions as a tumor suppressor in colon cancer by targeting DCLK3 and is therefore a promising therapeutic target for colon cancer.

摘要

背景

失调的微小RNA(miRNA)在人类癌症中很常见,并参与肿瘤细胞的增殖、进展和转移。因此,本研究旨在评估miR-1236-3p在结肠癌中的表达及生物学功能。

方法

本研究通过芯片分析筛选正常和结肠癌组织中的miRNA。此外,进行定量逆转录-聚合酶链反应(qRT-PCR)分析,以验证miR-1236-3p在结肠癌患者的正常和肿瘤组织以及癌细胞系中的表达。还采用在线预测算法和荧光素酶报告基因检测来确认双皮质素样激酶3(DCLK3)是miR-1236-3p的靶标。此外,评估了miR-1236-3p对结肠癌进展的影响。还进行了蛋白质印迹和qRT-PCR研究miR-1236-3p与DCLK3之间的相互作用。

结果

miR-1236-3p在结肠癌组织中显著下调,其表达与结肠癌的TNM分期和转移相关。此外,实验表明miR-1236-3p显著促进癌细胞凋亡,并抑制癌细胞的增殖、侵袭和迁移。结果还表明,miR-1236-3p通过靶向DCLK3阻碍上皮-间质转化(EMT)。此外,DCLK3的表达介导了miR-1236-3p对癌症进展的影响。

结论

miR-1236-3p通过靶向DCLK3在结肠癌中发挥肿瘤抑制作用,因此是结肠癌有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c08/8446622/2d1b62c22a13/fonc-11-688882-g001.jpg

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