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

The Journal of Clinical Investigation
Taotao HanJuan Shi

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 s...Continue Reading

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Citations

Dec 20, 2020·Microorganisms·Eleftherios KontizasDionyssios N Sgouras
Apr 2, 2021·Frontiers in Microbiology·Jinpu YangFeng Ji
May 15, 2021·Wiley Interdisciplinary Reviews. RNA·Nils Schmerer, Leon N Schulte
Jun 29, 2021·PeerJ·Zhihui ChenWeiwei Li
Dec 21, 2021·Frontiers in Cell and Developmental Biology·Shilang XiaoFen Wang

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Datasets Mentioned

BETA
GSE111762
GSE111763
GES-1
SRR10478832

Methods Mentioned

BETA
PCR
transfection
ChIP-Seq
ChIP
pull-down
immunoprecipitation
RIP
chromosomal aberrations
xenografts
biopsy

Software Mentioned

Cluster
client
CNkingbio
Linux
SPSS
gdc
Feature Extraction
Cytoscape
TreeView
GeneSpring GX

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