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Hsa_circ_0005100 通过 miR-145-5p/MACC1 轴调控结直肠癌的致瘤性。

Hsa_circ_0005100 regulates tumorigenicity of colorectal carcinoma via miR-145-5p/MACC1 axis.

机构信息

Department of Gastrointestinal Surgery, The Third Hospital Affiliated to Hebei Medical University, Shijiazhuang, China.

出版信息

J Clin Lab Anal. 2022 Aug;36(8):e24533. doi: 10.1002/jcla.24533. Epub 2022 Jun 29.

DOI:10.1002/jcla.24533
PMID:35766445
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9396189/
Abstract

BACKGROUND

Circular RNAs (circRNAs) are a kind of RNA molecules involved in the regulation of cancer progression, including colorectal carcinoma (CRC); nevertheless, their regulation mode is blurry. In the present work, we attempted to reveal the characteristics of hsa_hsa_circ_0005100 in CRC.

METHODS

Differential expressions of hsa_circ_0005100, FMN2 mRNA, microRNA-145-5p (miR-145-5p), and MACC1 were indicated by qRT-PCR and Western blot. The capacities of cell growth and motility were validated by the MTT assay, flow cytometry assay, EdU assay, colony formation assay, and transwell assay. Moreover, the targeted relationship of miR-145-5p and hsa_circ_0005100 or MACC1 was distinguished by dual-luciferase reporter assay. The animal experiment was implemented to confirm the influence of hsa_circ_0005100 on tumorigenesis in vivo.

RESULTS

Hsa_circ_0005100 and MACC1 expression levels were increased, but miR-145-5p expression level was diminished in CRC. Hsa_circ_0005100 knockdown repressed cell proliferation, cell cycle, migration, and invasion, while expedited cell apoptosis in CRC cells. Furthermore, miR-145-5p was disclosed to block CRC via overturning MACC1. Hsa_circ_0005100 targeted miR-145-5p to modulate MACC1. Additionally, hsa_circ_0005100 knockdown also attenuated tumorigenesis in vivo.

CONCLUSION

Hsa_circ_0005100 was a vital regulator in the development of CRC by miR-145-5p/MACC1 axis, which deepened the understanding of CRC pathogenesis from circRNA insights.

摘要

背景

环状 RNA(circRNA)是一类参与调控癌症进展的 RNA 分子,包括结直肠癌(CRC);然而,其调控模式尚不清楚。在本研究中,我们试图揭示 hsa_hsa_circ_0005100 在 CRC 中的特征。

方法

通过 qRT-PCR 和 Western blot 检测 hsa_circ_0005100、FMN2mRNA、微小 RNA-145-5p(miR-145-5p)和 MACC1 的差异表达。通过 MTT 检测、流式细胞术检测、EdU 检测、集落形成检测和 Transwell 检测验证细胞生长和迁移能力。此外,通过双荧光素酶报告基因检测区分 miR-145-5p 与 hsa_circ_0005100 或 MACC1 的靶向关系。通过动物实验证实 hsa_circ_0005100 对体内肿瘤发生的影响。

结果

CRC 中 hsa_circ_0005100 和 MACC1 的表达水平升高,而 miR-145-5p 的表达水平降低。hsa_circ_0005100 下调抑制 CRC 细胞的增殖、细胞周期、迁移和侵袭,同时促进细胞凋亡。此外,miR-145-5p 通过逆转 MACC1 被揭示为抑制 CRC 的作用因子。hsa_circ_0005100 靶向 miR-145-5p 来调节 MACC1。此外,hsa_circ_0005100 下调也减弱了体内的肿瘤发生。

结论

hsa_circ_0005100 通过 miR-145-5p/MACC1 轴在 CRC 的发展中是一个重要的调节因子,从 circRNA 的角度加深了对 CRC 发病机制的理解。

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