H. pylori infection alters repair of DNA double-strand breaks via SNHG17
Taotao Han, … , Jiazeng Sun, Juan Shi
Taotao Han, … , Jiazeng Sun, Juan Shi
Published June 15, 2020
Citation Information: J Clin Invest. 2020;130(7):3901-3918. https://doi.org/10.1172/JCI125581.
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Research Article Gastroenterology Oncology

H. pylori infection alters repair of DNA double-strand breaks via SNHG17

Abstract

Chronic infections can lead to carcinogenesis through inflammation-related mechanisms. Chronic infection of the human gastric mucosa with Helicobacter pylori is a well-known risk factor for gastric cancer. However, the mechanisms underlying H. pylori–induced gastric carcinogenesis are incompletely defined. We aimed to screen and clarify the functions of long noncoding RNAs (lncRNAs) that are differentially expressed in H. pylori–related gastric cancer. We found that lncRNA SNHG17 was upregulated by H. pylori infection and markedly increased the levels of double-strand breaks (DSBs). SNHG17 overexpression correlated with poor overall survival in patients with gastric cancer. The recruitment of NONO by overabundant nuclear SNHG17, along with the role of cytoplasmic SNHG17 as a decoy for miR-3909, which regulates Rad51 expression, shifted the DSB repair balance from homologous recombination toward nonhomologous end joining. Notably, during chronic H. pylori infection, SNHG17 knockdown inhibited chromosomal aberrations. Our findings suggest that spatially independent deregulation of the SNHG17/NONO and SNHG17/miR-3909/RING1/Rad51 pathways upon H. pylori infection promotes tumorigenesis in gastric cancer by altering the DNA repair system, which is critical for the maintenance of genomic stability. Upregulation of SNHG17 by H. pylori infection might be an undefined link between cancer and inflammation.

Authors

Taotao Han, Xiaohui Jing, Jiayu Bao, Lianmei Zhao, Aidong Zhang, Renling Miao, Hui Guo, Baoguo Zhou, Shang Zhang, Jiazeng Sun, Juan Shi

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Figure 9

SNHG17 interacts with miR-3909.

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SNHG17 interacts with miR-3909. (A) Western blot analysis of Rad51 expre...
(A) Western blot analysis of Rad51 expression upon H. pylori with SNHG17 knockdown. Samples were assayed more than 3 times. (B) Western blot analysis of Rad51 in cells expressing the indicated shRNA in the presence or absence of MG-132 treatment. Samples were assayed more than 3 times. (C) Bioinformatics predicted miR-3909 and RING1-binding sites in SNHG17 sequence. Partial sequences of SNHG17 and RING1 3′ UTR are shown. (D) qRT-PCR analysis of the expression levels of pri-miR-3909, pre-miR-3909, and mature miR-3909 in SGC-7901 cells overexpressing SNHG17. (E) qRT-PCR analysis for SNHG17 expression in SGC-7901 cells transfected for 24 hours with miR-NC, miR-3909 mimics, miR-NC inhibitor, and miR-3909 inhibitor. Data are presented as mean ± SEM. n = 3. *P < 0.05, 2-tailed Student’s t test.