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环状 RNA PTK2 通过 miR-139-3p 促进胃癌细胞增殖并抑制细胞凋亡。

Circular RNA PTK2 Accelerates Cell Proliferation and Inhibits Cell Apoptosis in Gastric Carcinoma via miR-139-3p.

机构信息

Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Air Force Medical University, Xi'an, 710032, Shaanxi, China.

Department of Internal Medicine No. 2, 4th (Xinyuan) Hospital of Yulin, No. 33, Renmin Middle Road, Yulin, 719000, Shaanxi, China.

出版信息

Dig Dis Sci. 2021 May;66(5):1499-1509. doi: 10.1007/s10620-020-06358-4. Epub 2020 Jun 5.

Abstract

BACKGROUND

Gastric carcinoma (GC) is one of the most common malignant tumors. Although increasing studies have indicated that circular RNAs function as ideal biomarkers for multiple cancers, only a few researches elucidated the correlation between circular RNA PTK2 (circPTK2) and human cancers.

AIM

To further explore the expression status, biological function, and regulatory mechanism of circPTK2 in GC.

METHODS

Bioinformatics analysis and function or mechanism experiments including RT-qPCR, flow cytometry, Western blot, luciferase reporter assay, and xenografts assays were applied to investigate the function of circPTK2 and miR-139-3p.

RESULTS

High expression of circPTK2 was presented in GC tissues and cells. The circPTK2 knockdown notably suppressed cell proliferation and promoted cell apoptosis in GC. In mechanism, circPTK2 served as a sponge of miR-139-3p. Inhibition of miR-139-3p could reverse circPTK2 silence-mediated effects on GC cell proliferation and apoptosis. Furthermore, the xenograft tumor model was established to investigate the role of circPTK2 in GC tumor growth. Experimental results delineated that the reduction in tumor growth in response to circPTK2 knockdown was partly recovered by miR-139-3p inhibitor.

CONCLUSIONS

CircPTK2 promotes GC development by sponging miR-139-3p, which may function as an effective gene target for managing GC.

摘要

背景

胃癌(GC)是最常见的恶性肿瘤之一。尽管越来越多的研究表明环状 RNA 可作为多种癌症的理想生物标志物,但仅有少数研究阐明了环状 RNA 原肌球蛋白激酶 2(circPTK2)与人类癌症之间的相关性。

目的

进一步探讨 circPTK2 在 GC 中的表达状态、生物学功能和调控机制。

方法

应用生物信息学分析和功能或机制实验,包括 RT-qPCR、流式细胞术、Western blot、荧光素酶报告基因检测和异种移植实验,研究 circPTK2 和 miR-139-3p 的功能。

结果

GC 组织和细胞中存在高表达的 circPTK2。circPTK2 敲低显著抑制 GC 细胞增殖并促进细胞凋亡。在机制上,circPTK2 可作为 miR-139-3p 的海绵。抑制 miR-139-3p 可逆转 circPTK2 沉默对 GC 细胞增殖和凋亡的影响。此外,建立了异种移植肿瘤模型以研究 circPTK2 在 GC 肿瘤生长中的作用。实验结果表明,circPTK2 敲低导致的肿瘤生长减少部分被 miR-139-3p 抑制剂恢复。

结论

circPTK2 通过海绵吸附 miR-139-3p 促进 GC 发展,可能作为治疗 GC 的有效基因靶点。

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