Hsa_circ_0079557 通过 hsa_circ_0079557/miR-502-5p/CCND1 轴促进结直肠癌细胞增殖。

Hsa_circ_0079557 Promotes the Proliferation of Colorectal Cancer Cells Through the hsa_circ_0079557/miR-502-5p/CCND1 Axis.

机构信息

Department of General Surgery, Zhujiang Hospital, Southern Medical University, Guangzhou, P.R. China.

Department of Gastrointestinal Sugery, First Quanzhou Hospital, Fujian Medical University, Quanzhou, P.R. China.

出版信息

Cancer Genomics Proteomics. 2023 Nov-Dec;20(6):567-581. doi: 10.21873/cgp.20406.

DOI:10.21873/cgp.20406

PMID:37889059

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10614065/

Abstract

BACKGROUND/AIM: Recent studies have demonstrated the crucial regulatory roles of circular RNAs (circRNAs) in cancer initiation and progression. The sponge mechanism of circRNAs has been shown to be widely active in various types of tumors. However, many circRNAs still have not been verified to function through this mechanism. This study aimed to investigate the regulatory mechanism of hsa_circ_0079557 in colorectal cancer (CRC) and its role in CRC progression.

MATERIALS AND METHODS

Raw gene expression profile datasets were downloaded from Gene Expression Omnibus (GEO) and combined to form a new dataset. Hsa_circ_0079557 was found to be highly expressed in CRC. Its role was evaluated in vitro and in vivo through a series of experiments, including quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, colony formation, cell counting kit-8 (CCK-8), transwell assays, scratch wound healing assays, nude mice experiments, and immunohistochemistry (IHC). The association between hsa_circ_0079557 and the identified target microRNAs (miRNA) was confirmed through fluorescence in situ hybridization (FISH) and dual-luciferase reporter assays. The downstream target proteins were predicted using the web-based tool "TargetScan," and their expressions were determined using Western blot (WB).

RESULTS

Hsa_circ_0079557 was found to be relatively up-regulated in CRC tissues and cell lines. Suppression of hsa_circ_0079557 expression inhibited cell proliferation in vitro and in vivo. Additionally, hsa_circ_0079557 acted as a "molecular sponge" for miR-502-5p, up-regulating the expression of Cyclin D1 (CCND1).

CONCLUSION

In this study, we identify a highly expressed circRNA in CRC and propose a novel pathway of hsa_circ_0079557/miR-502-5p/CCND1 in CRC.

摘要

背景/目的：最近的研究表明，环状 RNA（circRNAs）在癌症的发生和发展中具有关键的调节作用。circRNAs 的海绵机制已被证明在多种类型的肿瘤中广泛活跃。然而，许多 circRNAs 的功能仍未通过这种机制得到验证。本研究旨在探讨 hsa_circ_0079557 在结直肠癌（CRC）中的调节机制及其在 CRC 进展中的作用。

材料和方法

从基因表达综合数据库（GEO）下载原始基因表达谱数据集，并将其组合形成一个新的数据集。发现 hsa_circ_0079557 在 CRC 中高度表达。通过一系列实验，包括实时定量聚合酶链反应（qRT-PCR）、流式细胞术、集落形成、细胞计数试剂盒-8（CCK-8）、Transwell 测定、划痕愈合测定、裸鼠实验和免疫组织化学（IHC），在体外和体内评估了其作用。通过荧光原位杂交（FISH）和双荧光素酶报告基因检测证实了 hsa_circ_0079557 与鉴定的靶微小 RNA（miRNA）之间的关联。使用基于网络的工具“TargetScan”预测下游靶蛋白，并通过 Western blot（WB）确定其表达。