A Genetic Variant Located in <i>miR-146b</i> Promoter Region Is Associated with Prognosis of Gastric Cancer

Wang, Weizhi; Du, Mulong; Li, Zheng; Zhang, Lei; Li, Qing; Xu, Zhipeng; Li, Bowen; Wang, Linjun; Li, Fengyuan; Zhang, Diancai; Xu, Hao; Yang, Li; Gong, Weida; Fu, Qiang; Zhang, Zhengdong; Xu, Zekuan

doi:10.1158/1055-9965.epi-17-1054

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…We considered 10 patients with active nonatrophic chronic gastritis, 9 patients with intestinal metaplasia, 11 with dysplasia (low and high grade), and 9 patients with gastric adenocarcinoma, thus including all the lesions that define the carcinogenetic process of the intestinal variant of GC (i.e., the Correa's cascade). The expression of let-7i-5p, miR-146b-5p, and -185-5p was increased in GC samples and the early neoplastic condition (dysplasia), confirming results obtained by meta-analysis approach and in accordance to several works demonstrating the importance of these miRNAs in different tumors [ Figure 6A; (33)(34)(35)(36)(37)(38)]. Despite meta-analysis results that revealed that let-7f-5p increased, we did not confirm such an alteration in our samples.…”

Section: Mirnas Targeting the Ciita Mrna Are Up-regulated In Gcsupporting

confidence: 89%

Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA

et al. 2020

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Macrophages have a major role in infectious and inflammatory diseases, and the available data suggest that Helicobacter pylori persistence can be explained in part by the failure of the bacterium to be killed by professional phagocytes. Macrophages are cells ready to kill the engulfed pathogen, through oxygen-dependent and-independent mechanisms; however, their killing potential can be further augmented by the intervention of T helper (Th) cells upon the specific recognition of human leukocyte antigen (HLA)-II-peptide complexes on the surface of the phagocytic cells. As it pertains to H. pylori, the bacterium is engulfed by macrophages, but it interferes with the phagosome maturation process leading to phagosomes with an altered degradative capacity, and to megasomes, wherein H. pylori resists killing. We recently showed that macrophages infected with H. pylori strongly reduce the expression of HLA-II molecules on the plasma membrane and this compromises the bacterial antigen presentation to Th lymphocytes. In this work, we demonstrate that H. pylori hampers HLA-II expression in macrophages, activated or non-activated by IFN-γ, by down-regulating the expression of the class II major histocompatibility complex transactivator (CIITA), the "master control factor" for the expression of HLA class II genes. We provided evidence that this effect relies on the up-regulation of let-7f-5p, let-7i-5p, miR-146b-5p, and-185-5p targeting CIITA. MiRNA expression analysis performed on biopsies from H. pylori-infected patients confirmed the up-regulation of let-7i-5p, miR-146b-5p, and-185-5p in gastritis, in pre-invasive lesions, and in gastric cancer. Taken together, our results suggest that specific miRNAs may be directly involved in the H. pylori infection persistence and may contribute to confer the risk of developing gastric neoplasia in infected patients.

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Section: Mirnas Targeting the Ciita Mrna Are Up-regulated In Gcsupporting

confidence: 89%

Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA

et al. 2020

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“…Chen, Jiang, et al, 2017;L. Li, Pan, et al, 2013;Liu et al, 2012;Qi et al, 2014;Sadeghi et al, 2018;Wang et al, 2014Wang et al, , 2018Yang et al, 2019;Yin et al, 2018).…”

Section: Risk Snps In Mirna Promoters/enhancersunclassified

Noncoding RNA mutations in cancer

et al. 2023

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Cancer is driven by both germline and somatic genetic changes. Efforts have been devoted to characterizing essential genetic variations in cancer initiation and development. Most attention has been given to mutations in protein‐coding genes and associated regulatory elements such as promoters and enhancers. The development of sequencing technologies and in silico and experimental methods has allowed further exploration of cancer predisposition variants and important somatic mutations in noncoding RNAs, mainly for long noncoding RNAs and microRNAs. Association studies including GWAS have revealed hereditary variations including SNPs and indels in lncRNA or miRNA genes and regulatory regions. These mutations altered RNA secondary structures, expression levels, and target recognition and then conferred cancer predisposition to carriers. Whole‐exome/genome sequencing comparing cancer and normal tissues has revealed important somatic mutations in noncoding RNA genes. Mutation hotspots and somatic copy number alterations have been identified in various tumor‐associated noncoding RNAs. Increasing focus and effort have been devoted to studying the noncoding region of the genome. The complex genetic network of cancer initiation is being unveiled.This article is categorized under: RNA in Disease and Development > RNA in Disease

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“…GCa patients without obvious symptoms cannot be diagnosed at an early stage but usually exhibit rapid progression, so finding biomarkers with early predictive value for guiding individualized treatment is a worldwide focus. Although clinical factors have been demonstrated as important prognostic predictors for GCa patients' survival, 2,3 germline variants inherited from parents have been deemed able to explain the survival difference among patients to a great extent 4,5 . Previous reports have indicated that genetic variants in DNA repair pathways might affect patient survival due to modifying chemotherapy efficacy 6,7 .…”

Section: Introductionmentioning

confidence: 99%

“…Although clinical factors have been demonstrated as important prognostic predictors for GCa patients' survival, 2,3 germline variants inherited from parents have been deemed able to explain the survival difference among patients to a great extent. 4,5 Previous reports have indicated that genetic variants in DNA repair pathways might affect patient survival due to modifying chemotherapy efficacy. 6,7 In addition, genes known to drive the tumorigenesis, proliferation, invasiveness and metastasis ability of cancer cells (eg, nuclear factor-kappa b [NF-κB], Yes-associated protein [YAP], 8 and mammalian target of rapamycin [mTOR]) also harbor genetic variants that influence the death risk of GCa patients, as indicated by our previous work.…”

Section: Introductionmentioning

confidence: 99%

Remote modulation of WWOX by an intronic variant associated with survival of Chinese gastric cancer patients

Cheng,

Chang,

Xia

et al. 2023

Intl Journal of Cancer

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The protein WWOX was reported to be involved in cancer progression via interaction with mTOR and DNA repair pathway. We previously reported noteworthy association of some single nucleotide polymorphisms (SNPs) in mTOR and DNA repair pathways with gastric cancer (GCa) patients' survival. We hypothesized that genetic variants in WWOX gene could predict the survival of GCa patients. By extracting WWOX genetic variants from our ongoing genome‐wide association study including 796 GCa patients from an Eastern Chinese population, we identified 51 out of 1913 SNPs to be significantly associated with survival of GCa patients, which passed the false positive probability tests. In particular, the intronic variant rs9922483, a G>T change, was associated with 21% increased death risk for GCa patients (HR = 1.21, 95% CI = 1.04‐1.42, P = .015). This locus was predicted to be involved in potential enhancer by bioinformatics analysis. Genotype‐phenotype correlation analysis revealed decreased expression of WWOX by rs9922483 G>T change. Mechanistically, rs9922483 locus may exhibits long‐range interaction with WWOX promoter, and the G>T change inhibited the transcriptional activity driven by WWOX promoter in luciferase reporter system. Especially, the G>T change had an allele‐specific negative effect on NR3C1 binding, and NR3C1 promoted the expression of WWOX in GCa cells. Further functional analysis indicated an increase in proliferation, migration and invasion of GCa cells by knockdown of WWOX. In conclusion, WWOX genetic variants may modulate survival of Chinese GCa patients by exerting remote regulatory effect on WWOX expression. Our results highlight the cis‐regulatory effect of genetic variants on genes and survival modulation for GCa patients.

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A Genetic Variant Located in miR-146b Promoter Region Is Associated with Prognosis of Gastric Cancer

Cited by 8 publications

References 23 publications

Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA

Helicobacter pylori Dampens HLA-II Expression on Macrophages via the Up-Regulation of miRNAs Targeting CIITA

Noncoding RNA mutations in cancer

Remote modulation of WWOX by an intronic variant associated with survival of Chinese gastric cancer patients

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