环状 RNA PABPC1 通过与整合素连接激酶相互作用激活 NF-κB 通路促进胃癌的恶性进展。

Circ_PABPC1 promotes the malignancy of gastric cancer through interacting with ILK to activate NF-κB pathway.

机构信息

Departments of Oncology, The Second Xiangya Hospital of Central-South University, Changsha, Hunan, 410011, China; Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China.

Departments of Radiotherapy, Hunan Provincial Hospital of Integrated Chinese and Western Medicine, The Affiliated Hospital of Hunan Academy of Traditional Chinese Medicine, Changsha, Hunan, 410006, China.

出版信息

Exp Cell Res. 2024 May 15;438(2):114058. doi: 10.1016/j.yexcr.2024.114058. Epub 2024 Apr 28.

DOI:10.1016/j.yexcr.2024.114058

PMID:38688434

Abstract

BACKGROUND

Gastric cancer (GC) is a common cancer type with both high incidence and mortality. Recent studies have revealed an important role of circRNA in the development of GC. However, more experiments are needed to reveal the precise molecular mechanisms of circRNA in GC development.

METHODS

Bioinformatics analysis was conducted to predict the potential role of circ_PABPC1 in GC and the target proteins of circ_PABPC1. Quantitative RT-PCR, Western blot and immunohistochemistry assays were conducted to detect the levels of circ_PABPC1, NF-κB p65, NF-κB p65 (Ser536) and ILK. MTT, Edu staining, cell scratch-wound and trans-well assays were carried out to detect cell proliferation, migration and invasion. The interaction between ILK and circ_PABPC1 was confirmed by RNA immunoprecipitation (RIP), RNA pull-down and fluorescence in situ hybridization assays. Genetically modified GC cells were injected into mice to evaluate the tumor growth performance.

RESULTS

This study found that the high expression of circ_PABPC1 was associated with a poor prognosis of GC. The up-regulation of circ_PABPC1 promoted the proliferation, migration and invasion of GC cells. Circ_PABPC1 bound to ILK protein, thereby preventing the degradation of ILK. ILK mediated the effect of circ_PABPC1 on GC cells through activating NF-κB.

CONCLUSION

circ_PABPC1 promotes the malignancy of GC cells through binding to ILK to activate NF-κB signaling pathway.

摘要

背景

胃癌（GC）是一种发病率和死亡率都很高的常见癌症类型。最近的研究表明，circRNA 在 GC 的发生发展中起重要作用。然而，还需要更多的实验来揭示 circRNA 在 GC 发展中的精确分子机制。

方法

通过生物信息学分析预测 circ_PABPC1 在 GC 中的潜在作用及其靶蛋白。采用定量 RT-PCR、Western blot 和免疫组织化学检测 circ_PABPC1、NF-κB p65、NF-κB p65（Ser536）和 ILK 的水平。通过 MTT、Edu 染色、细胞划痕和 Transwell 实验检测细胞增殖、迁移和侵袭。通过 RNA 免疫沉淀（RIP）、RNA 下拉和荧光原位杂交实验证实了 ILK 和 circ_PABPC1 之间的相互作用。通过将遗传修饰的 GC 细胞注射到小鼠中来评估肿瘤生长性能。