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Hsa_circ_0002019 通过调节 TNFAIP6/NF-κB 信号通路促进胃癌细胞的增殖、迁移和侵袭。

Hsa_circ_0002019 promotes cell proliferation, migration, and invasion by regulating TNFAIP6/NF-κB signaling in gastric cancer.

机构信息

Department of Gastroenterology, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China.

Department of Hepatobiliary and Pancreatic Gastroenterology, Jinhua People's Hospital, Jinhua 321000, Zhejiang Province, China.

出版信息

Genomics. 2023 Jul;115(4):110641. doi: 10.1016/j.ygeno.2023.110641. Epub 2023 May 16.

DOI:10.1016/j.ygeno.2023.110641
PMID:37201873
Abstract

BACKGROUND

Gastric cancer (GC) is a common cancer with a high incidence and mortality rate. Herein, the role of hsa_circ_0002019 (circ_0002019) in GC was investigated.

METHODS

The molecular structure and stability of circ_0002019 were identified by RNase R, and Actinomycin D treatment. Molecular associations were verified by RIP. Proliferation, migration, and invasion were detected by CCK-8, EdU, and Transwell, respectively. The effect of circ_0002019 on tumor growth was analyzed in vivo.

RESULTS

Circ_0002019 was elevated in GC tissues and cells. Circ_0002019 knockdown inhibited the proliferation, migration, and invasion. Mechanically, circ_0002019 activated NF-κB signaling by increasing TNFAIP6 mRNA stability by PTBP1. Activation of NF-κB signaling limited the antitumor effect of circ_0002019 silencing in GC. Circ_0002019 knockdown inhibited tumor growth in vivo by reducing TNFAIP6 expression.

CONCLUSIONS

Circ_0002019 accelerated the proliferation, migration, and invasion by regulating TNFAIP6/NF-κB pathway, suggesting circ_0002019 could be a key regulatory factor in GC progression.

摘要

背景

胃癌(GC)是一种常见的癌症,发病率和死亡率都很高。在此,研究了 hsa_circ_0002019(circ_0002019)在 GC 中的作用。

方法

通过 RNase R 和 Actinomycin D 处理鉴定 circ_0002019 的分子结构和稳定性,并通过 RIP 验证分子关联。通过 CCK-8、EdU 和 Transwell 分别检测增殖、迁移和侵袭。在体内分析 circ_0002019 对肿瘤生长的影响。

结果

circ_0002019 在 GC 组织和细胞中升高。circ_0002019 敲低抑制增殖、迁移和侵袭。机制上,circ_0002019 通过增加 PTBP1 介导的 TNFAIP6 mRNA 稳定性来激活 NF-κB 信号。NF-κB 信号的激活限制了 circ_0002019 沉默在 GC 中的抗肿瘤作用。circ_0002019 敲低通过降低 TNFAIP6 表达抑制体内肿瘤生长。

结论

circ_0002019 通过调节 TNFAIP6/NF-κB 通路加速增殖、迁移和侵袭,表明 circ_0002019 可能是 GC 进展的关键调节因子。

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