Genetic variants in N6-methyladenosine are associated with bladder cancer risk in the Chinese population

Liu, Hanting; Gu, Jingjing; Jin, Yu; Qi, Yuan; Ma, Gaoxiang; Du, Mulong; Ge, Yuqiu; Qin, Chao; Lv, Qiang; Fu, Guangbo; Wang, Meilin; Chu, Haiyan; Lin, Yuan; Zhang, Zhengdong

doi:10.1007/s00204-020-02911-2

Cited by 20 publications

(24 citation statements)

References 40 publications

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“…For patients with non-muscle invasive tumors (NMIBC), transurethral resection combined with postoperative bladder perfusion chemotherapy or BCG treatment strategies is usually adopted ( Charpentier et al, 2021 ; Li et al, 2021e ). However, 20–30% of NMIBC patients will progress to muscle invasive bladder cancer (MIBC), and 50% will develop distant metastases within 2 years of radical surgery ( Jiang et al, 2021a ; Liu et al, 2021a ). For locally advanced or advanced MIBC patients, gemcitabine combined with cisplatin (GC regimen) remains the standard treatment, however, BC fatality rates have only dropped by 1.5% in the past 15 years ( Kaur et al, 2021 ; Roviello et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Liu

2022

Front. Genet.

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N6-methyladenosine (m6A) is a dynamic, reversible post-transcriptional modification, and the most common internal modification of eukaryotic messenger RNA (mRNA). Considerable evidence now shows that m6A alters gene expression, thereby regulating cell self-renewal, differentiation, invasion, and apoptotic processes. M6A methylation disorders are directly related to abnormal RNA metabolism, which may lead to tumor formation. M6A methyltransferase is the dominant catalyst during m6A modification; it removes m6A demethylase, promotes recognition by m6A binding proteins, and regulates mRNA metabolic processes. Bladder cancer (BC) is a urinary system malignant tumor, with complex etiology and high incidence rates. A well-differentiated or moderately differentiated pathological type at initial diagnosis accounts for most patients with BC. For differentiated superficial bladder urothelial carcinoma, the prognosis is normally good after surgery. However, due to poor epithelial cell differentiation, BC urothelial cell proliferation and infiltration may lead to invasive or metastatic BC, which lowers the 5-years survival rate and significantly affects clinical treatments in elderly patients. Here, we review the latest progress in m6A RNA methylation research and investigate its regulation on BC occurrence and development.

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Section: Introductionmentioning

confidence: 99%

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Liu

2022

Front. Genet.

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“…9,10 Recently, m6A-SNPs have attracted considerable attention, and a number of prioritized SNPs have been identified by integrative analysis of cancer-related GWAS summary data, including in pancreatic, bladder, and gastric cancers. [11][12][13] The aim of the present study was to shed light and explore the potential contribution of m6A-SNPs in CRC pathogenesis.…”

Section: Introductionmentioning

confidence: 99%

Genome-Wide Identification of m6A-Associated Single-Nucleotide Polymorphisms in Colorectal Cancer

Zhao¹,

Jiang²,

Wang³

et al. 2021

PGPM

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Background: N6-methyladenosine (m6A)-associated single-nucleotide polymorphisms (SNPs) play important roles in cancers, with previous research suggesting potential associations between m6A-SNPs and cancer. However, the relationship between the genetic determinants of m6A modification and colorectal cancer (CRC) remains unclear. Methods: An integrative method combining raw data and summary statistics of genomewide association studies with expression quantitative trait loci (eQTL) and differential expression data was applied to screen potential candidate CRC-associated m6A-SNPs. Results: A total of 402 m6A-SNPs were identified as being associated with CRC (p < 0.001), with 98 showing eQTL signals. In particular, three genes were found to harbor CRCassociated m6A-SNPs: rs178184 in NOVA1, rs35782901 in HTR4, and rs60571683 in SLCO1B3. These genes were differentially expressed in at least one publicly available dataset (p < 0.05), with NOVA1 (p = 3.41×10 −11 ) and HTR4 (p = 5.56×10 −7 ) being significantly downregulated in CRC (dataset: GSE89076), and SLCO1B3 was significantly overexpressed (datasets: GSE32323 [p = 3.27×10 −5 ], GSE21510 [p = 1.09×10 −6 ], and GSE89076 [p = 7.63×10 −6 ]). Conclusion:This study identified three m6A-SNPs (rs178184, rs35782901, and rs60571683) that may be associated with CRC. However, the lack of analysis of primary CRC samples in order to further elucidate the underlying pathogenesis is a major limitation of this study. Future investigations are needed to validate these CRC-associated m6A-SNPs and explore the m6A-mediated pathogenic mechanism in CRC.

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“…Recently, it has been confirmed that m 6 A modified disorders are involved in human carcinogenesis, including osteosarcoma [ 28 ], glioblastoma [ 29 ], colorectal cancer [ 30 ], acute myeloid leukemia [ 31 ], gastric cancer [ 32 ], glioma [ 33 ], and bladder cancer [ 34 ]. The abnormal modification level of m 6 A may affect the individual’s cancer susceptibility [ 35 ]. YTH domain contains protein 1 (YTHDC1), an important m 6 A recognition protein, is involved in mRNA splicing and the export of methylated mRNAs [ 36 , 37 ], but its role has not yet been deeply understood.…”

Section: Introductionmentioning

confidence: 99%

YTHDC1 gene polymorphisms and neuroblastoma susceptibility in Chinese children

Wang

et al. 2021

Aging

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Neuroblastoma (NB) is the most common extracranial tumor in children. YTHDC1, a member of RNA methylation modification binding proteins, plays critical roles in tumor occurrence and metastasis. However, it is unclear whether YTHDC1 gene polymorphisms are related to NB susceptibility. Herein, we aimed to evaluate the association between YTHDC1 gene polymorphisms (rs2293596 T>C, rs2293595 T>C, rs3813832 T>C) and susceptibility of NB by logistic regression models. In this eight-center case-control study, 898 patients with NB and 1734 healthy controls were genotyped by TaqMan assay. The results showed that rs3813832 TC genotype could significantly reduce the susceptibility of NB compared with the TT genotype [adjusted odds ratio (AOR) = 0.81, 95% confidence interval (CI) = 0.68–0.96, P = 0.018]. Combined genotype analysis revealed that individuals with 3 protective genotypes had a prominently lower NB risk than those with 0-2 protective genotypes (AOR = 0.80, 95% CI = 0.68–0.94, P = 0.006). The stratified analysis also demonstrated the protective effect of rs3813832 TC/CC and 3 protective genotypes in certain subgroups. Further functional experiments revealed that YTHDC1 siRNA-554, targeting the area near the rs3813832 T>C polymorphism site, could observably inhibit the proliferation and migration of NB cells. In conclusion, our findings highlight the involvement of YTHDC1 gene and its genetic variants in the etiology of NB.

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Genetic variants in N6-methyladenosine are associated with bladder cancer risk in the Chinese population

Cited by 20 publications

References 40 publications

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Current Advances in N6-Methyladenosine Methylation Modification During Bladder Cancer

Genome-Wide Identification of m6A-Associated Single-Nucleotide Polymorphisms in Colorectal Cancer

YTHDC1 gene polymorphisms and neuroblastoma susceptibility in Chinese children

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