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环状 RNA RIP2 通过负向调控 CBFB 加剧结直肠癌的恶化。

CircRIP2 aggravates the deterioration of colorectal carcinoma by negatively regulating CBFB.

机构信息

Department of Oncology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.

出版信息

Eur Rev Med Pharmacol Sci. 2022 May;26(10):3514-3521. doi: 10.26355/eurrev_202205_28846.

Abstract

OBJECTIVE

This study aims to detect expression pattern and clinical significance of circRIP2 in colorectal carcinoma (CRC). In the meantime, the regulatory effect of circRIP2 on CRC cell functions is clarified.

PATIENTS AND METHODS

Relative levels of circRIP2 in 45 cases of CRC tissues and paracancerous tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Its clinical significance in predicting pathological manifestations of CRC was analyzed. In vitro regulation of circRIP2 on proliferative and migratory abilities of Sw620 and HCT-116 cells was assessed by cell counting kit-8 (CCK-8), 5-Ethynyl-2'-deoxyuridine (EdU) and transwell assay, respectively. Dual-Luciferase reporter assay and rescue experiments were conducted to reveal the interaction between circRIP2 and its target gene CBFB, as well as their co-regulation on CRC cell functions. At last, in vivo regulation of circRIP2 on CRC growth in nude mice implanted with HCT-116 cells was explored.

RESULTS

CircRIP2 was upregulated in these samples of CRC tissues and cell lines. High level of circRIP2 predicted advanced staging, and high risk of distant metastasis of CRC. In vitro knockdown of circRIP2 weakened proliferative and migratory abilities in Sw620 and HCT-116 cells. CBFB was downregulated in CRC tissues, which was negatively regulated by circRIP2 as its target gene. The attenuated proliferative and migratory abilities in Sw620 and HCT-116 cells with circRIP2 knockdown were abolished by co-silence of circRIP2 and CBFB. Moreover, in vivo knockdown of circRIP2 slowed down CRC growth in nude mice, and upregulated positive expression of CBFB in xenografted CRC tissues.

CONCLUSIONS

CircRIP2 is a potential indicator for predicting tumor staging and distant metastasis of CRC. It aggravates the deterioration of CRC through negatively regulating CBFB.

摘要

目的

本研究旨在检测环状 RNA 相互作用蛋白 2(circRIP2)在结直肠癌(CRC)中的表达模式和临床意义。同时,阐明 circRIP2 对 CRC 细胞功能的调节作用。

方法

采用实时定量聚合酶链反应(qRT-PCR)检测 45 例 CRC 组织和癌旁组织中 circRIP2 的相对水平,分析其预测 CRC 病理表现的临床意义。通过细胞计数试剂盒-8(CCK-8)、5-乙炔基-2'-脱氧尿苷(EdU)和 Transwell 实验分别评估 circRIP2 对 Sw620 和 HCT-116 细胞增殖和迁移能力的体外调节作用。通过双荧光素酶报告基因实验和挽救实验揭示 circRIP2 与其靶基因 CBFB 之间的相互作用,以及它们对 CRC 细胞功能的共同调节作用。最后,探讨 circRIP2 对裸鼠皮下种植 HCT-116 细胞的 CRC 生长的体内调节作用。

结果

CRC 组织和细胞系中 circRIP2 表达上调。高水平的 circRIP2 预示着 CRC 分期较晚,且远处转移风险较高。体外敲低 circRIP2 可减弱 Sw620 和 HCT-116 细胞的增殖和迁移能力。CBFB 在 CRC 组织中下调,作为其靶基因受 circRIP2 负调控。circRIP2 敲低后 Sw620 和 HCT-116 细胞增殖和迁移能力的减弱被 circRIP2 和 CBFB 共沉默所消除。此外,体内敲低 circRIP2 可减缓裸鼠 CRC 的生长,并上调异种移植 CRC 组织中 CBFB 的阳性表达。

结论

circRIP2 是预测 CRC 分期和远处转移的潜在指标。它通过负调控 CBFB 加重 CRC 的恶化。

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