As a representative item of chemical carcinogen, MNNG is closely associated with the onset of gastric cancer (GC), where N6-methyladonosine (m6A) RNA methylation is recognized as a critical epigenetic event. In our previous study, we found that the m6A modification by methyltransferase METTL3 was up-regulated in MNNG-exposed malignant GES-1 cells (MC cells) compared to control cells in vitro, and long non-coding RNA SNHG7 as a downstream target of the METTL3. However, the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC remains unclear. In the present study, we continuously investigate the functional role of METTL3 in mediating the SNHG7 axis in MNNG-induced GC. RIP-PCR and m6A-IP-qPCR were used to examine the molecular mechanism underlying the METTL3/m6A/SNHG7 axis in MNNG-induced GC. A METTL3 knockout mice model was constructed and exposed by MNNG. Western blot analysis, IHC analysis, and RT-qPCR were used to measure the expression of METTL3, SNHG7, and EMT markers. In this study, we demonstrated that in MNNG-induced GC tumorigenesis, the m6A modification regulator METTL3 facilitates cellular EMT and biological functions through the m6A/SNHG7 axis using in vitro and in vivo models. In conclusion, our study provides novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.

As a representative example of an environmental chemical carcinogen, MNNG exposure is closely associated with the onset of gastric cancer (GC) where N6-methyladenosine (m6A) RNA methylation tends to be the critical epigenetic event. However, the effect of m6A modification on long non-coding RNAs (lncRNAs) in MNNG-induced GC onset is still unclear. To address the above issue, based on the Methylated RNA immunoprecipitation sequencing (MeRIP-seq) data of MNNG-induced malignant cells (MCs) and GC cells, we comprehensively analyzed the MNNG exposure-associated vital lncRNAs. MeRIP-seq analysis identified 1432 lncRNA transcripts in the MC cell, and 3520 lncRNA transcripts were found to be m6A modified in the GC cell, respectively. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that MNNG exposure could spark cellular localization change, which might be the critical cellular note variation for malignant transformation. We demonstrated that METTL3 is responsible for N6 methylation of lncRNAs and identified SNHG7 as a downstream target of METTL3. More importantly, we observed that SNHG7 was progressively up-regulated during gastric carcinogenesis by MNNG exposure. Finally, we investigated SNHG7 expression in different stages of GC malignancies and found that elevated SNHG7 expression correlated with advanced clinical features and poor prognosis in GC. In conclusion, our study found for the first time that METTL3 regulates the m6A methylation level of lncRNA SNHG7 and its expression in MNNG exposure-induced GC, suggesting that SNHG7 as a predictive biomarker or therapeutic target for GC.

As the representative item of environmental chemical carcinogen, MNNG was closely associated with the onset of Gastric cancer (GC), while the underlying mechanisms remain largely unknown. Here, we comprehensively analyzed the potential clinical significance of METTL3 in multiple GC patient cohorts. Additionally, we demonstrated that long-term exposure to MNNG elevated METTL3 and EMT marker expression by in vitro and in vivo models. Furthermore, the depletion of METTL3 impacted the proliferation, migration, invasion, and tumorigenesis of MNNG malignant transformation cells and GC cells. By me-RIP sequencing, we identified a panel of vital miRNAs potentially regulated by METTL3 that aberrantly expressed in MNNG-induced GC cells. Mechanistically, we showed that METTL3 meditated miR-1184/TRPM2 axis by regulating the process of miRNA-118. Our results provide novel insights into critical epigenetic molecular events vital to MNNG-induced gastric carcinogenesis. These findings suggest the potential therapeutic targets of METTL3 for GC treatment.

目的:探讨胰岛素样生长因子2 mRNA结合蛋白2(insulin-like growth factor 2 mRNA binding pro-tein2,IGF2BP2)基因rs4402960、rs1 1705701、rs1470579和rs9877179的单核苷酸多态性(single nucleotide polymorphism,SNP)与胃癌发病风险的关联.方法:采用病例-对照研究的方法,收集甘肃省武威地区胃癌病例548例,健康对照706例;采用高通量Hi-SNP的方法对上述四个SNPs位点基因分型;采用x2检验和Logistic回归分析这四个SNPs与胃癌发病风险的关联.结果:IGF2BP2基因的rs9877179与胃癌发病风险的降低显著相关(P＜0.05);与TT/TG基因型携带者相比,rs9877179 GG基因型携带者的胃癌发病风险显著下降;分层分析发现,与T等位基因女性携带者相比,G等位基因女性携带者的胃癌发病风险显著下降;与TT/TG基因型携带者相比,GG基因型携带者患中晚期胃癌的风险显著下降.此外,未发现rs4402960、rs1 1705701和rs1470579与胃癌发病风险相关.结论:IGF2BP2基因的rs9877179与胃癌发病风险相关,其GG基因型和G等位基因可能是胃癌发生的保护因素.

Methyltransferase-like 3 (METTL3) and methyltransferase-like 14 (METTL14) were two core components of the N6-methyadenosine (m6A) methyltransferase complex (MTC) and played a basic role in maintaining an appropriate m6A level of target genes. In gastric cancer (GC), previous researches on the expression and role of METTL3 and METTL14 were not consistent, and their specific function and mechanism have remained elusive. In this study, the expression of METTL3 and METTL14 was evaluated based on the TCGA database, 9 paired GEO datasets, and our 33 GC patient samples, and METTL3 was highly expressed and acted as a poor prognostic factor, whereas METTL14 showed no significant difference. Moreover, GO and GSEA analyses were performed, and the results pointed out that METTL3 and METTL14 were jointly involved in multiple biological processes, while they could also take part in different oncogenic pathways independently. And BCLAF1 was predicted and identified as a novel shared target of METTL3 and METTL14 in GC. In total, we conducted a comprehensive analysis of METTL3 and METTL14 in GC including their expression, function, and role, which could provide a novel insight into the research of m6A modification in GC.

N6-methyladenosine (m6A) methylation, the most prevalent post-transcriptional modification in eukaryotes, represents a highly dynamic and reversible process that is regulated by m6A methyltransferases, m6A demethylases and RNA-binding proteins during RNA metabolism, which affects RNA function. Notably, m6A modification is significantly enriched in the brain and exerts regulatory roles in neurogenesis and neurodevelopment through various mechanisms, further influencing the occurrence and progression of neurological disorders. This study systematically summarizes and discusses the latest findings on common m6A regulators, examining their expression, function and mechanisms in neurodevelopment and neurological diseases. Additionally, we explore the potential of m6A modification in diagnosing and treating neurological disorders, aiming to provide new insights into the molecular mechanisms and potential therapeutic strategies for neurological disorders.

Background and purpose: Both HOTTIP and H19 are members of long non-coding RNA(lncRNA). They have been found to play an important role in the occurrence, development and migration of tumors. This study aimed to investigate the association between single nucleotide polymorphisms (SNP) of HOTTIP rs2067087, H19 rs2839698 and H19 rs2107425 and the risk of cervical lesions of different grades. Methods: The peripheral venous blood and related clinical data of 345 cases of cervical lesions were collected from Nov. 2018 to Dec. 2020 in Yancheng No.1 People's Hospital, including 220 cases of cervical intraepithelial neoplasia (CIN) and 125 cases of cervical cancer (CC). Three hundred and sixty patients without cervical lesions hospitalized during the same period were selected as the control. TaqMan real-time fluorescence quantitative polymerase chain reaction (RTFQPCR) was used to genotype the HOTTIP SNP rs2067087, H19 SNP rs2839698 and rs2107425 in the two groups, and χ2 test and unconditional logistic regression were used to analyze the association of the three SNP loci with cervical lesions of different grades. Results: Compared with the control group, there were significant differences in genotype distribution of HOTTIP rs2067087 and H19 rs2839698 in patients with cervical lesions. In the recessive model, the frequency of cervical lesions in patients with HOTTIP rs2067087 GG genotype increased by 52.2% (95% CI: 1.021-2.269, P<0.05). Stratified analysis showed that GG genotype at this locus mainly increased the risk of CIN (OR =1.730, 95% CI: 1.117-2.680, P<0.05); Stratified analysis showed that the GG genotype at this locus mainly increased the risk of CIN (OR=1.730, 95% CI:1.117-2.680, P<0.05). Compared with CC+CT genotype, the risk of cervical cancer in patients with H19 rs2839698 TT genotype was reduced by 70.8% (95% CI: 0.087-0.976, P<0.05). No correlation was found between H19 rs2107425 and cervical lesions of different grades (P>0.05). Conclusion: HOTTIP rs2067087 SNP is associated with different levels of cervical lesions, and the GG genotype may be a risk factor for CIN; H19 rs2839698 SNP is associated with the risk of cervical cancer, and the TT genotype may be a protective factor for cervical cancer.

The health risks caused by environmental pollution have long been of substantial concern. With the development of epigenetics, a large number of studies have demonstrated that N6-methyladenosine (m6A) modification is involved in the regulation of various important life activities associated with various diseases. Recent studies have revealed that m6A plays a key role in health damage caused by environmental exposure by regulating post-transcriptional gene expression. Therefore, our study outlined the effects of environmental pollutant exposure on m6A methylation and its regulator levels. Moreover, we found that m6A methylation modifications were involved in the development of various health damages by regulating important life activities in vivo, such as reactive oxygen species imbalance, apoptosis, epithelial–mesenchymal transition (EMT), and inflammatory processes. More importantly, we delved into the regulatory mechanisms of m6A methylation dysregulation in environmental pollution-induced diseases. Finally, by examining the published literature, we found that methyltransferase-like protein 3 (METTL3) and fat mass- and obesity-associated protein (FTO) were potentially used as biomarkers of health damage induced by particulate matter exposure and heavy metal exposure, respectively. The current studies on regulators of METTL3 and FTO were more promising to bring new perspectives for the treatment of environmental health-related diseases.

目的:探讨 MEG3 rs10132552 和 rs7158663 单核苷酸多态性(single nucleotide polymorphism,SNP)与不同宫颈病变患者发病风险的关系.方法:2018年11月到2020年11月,收集328例宫颈病变患者的外周静脉血及相关临床信息为病例,包括210例宫颈上皮内病变(cervical intraepithelial neoplasia,CIN)患者和118例宫颈癌(cervical cancer,CC)患者,以同期住院的345例无宫颈病变患者作为对照组,采用TaqMan RT-PCR方法进行基因分型,采用x2检验和logistic回归分析SNP位点与不同级别宫颈病变的相关性.结果:与对照组相比,MEG3 rs10132552 CT+CC基因型在宫颈病变组中分布频率显著降低(P＜0.05),其发病风险为0.701(95％CI:0.515～0.954);且在＞50岁患者中,携带MEG3 rs10132552 CT+CC基因型发生宫颈病变的风险显著降低(OR=0.634,95％CI:0.412～0.978,P＜0.05).将宫颈病变组分为宫颈上皮内病变组和宫颈癌组进行分层分析发现,该位点CT+CC基因型主要降低了宫颈癌组的发病风险(OR=0.520,95％CI:0.333～0.811,P＜0.05);进一步进行临床进展相关性分析,未发现MEG3 rs10132552与不同级别宫颈上皮内病变、不同病理类型、临床分期的宫颈癌具有相关性(P＞0.05).未发现MEG3 rs7158663位点与不同级别宫颈病变具有相关性(P＞0.05).结论:MEG3 rs10132552 SNP与宫颈癌的发病风险相关,其CT+CC基因型可能是宫颈癌发生的保护因素.

As one of the most common forms of RNA modification, N6-methyladenosine (m6A) RNA modification has attracted increasing research interest in recent years. This reversible RNA modification added a new dimension to the post-transcriptional regulation of gene expression. In colorectal cancer (CRC), the role of m6A modification has been extensively studied, not only on mRNAs but also on non-coding RNAs (ncRNAs). In the present review, we depicted the role of m6A modification in CRC, systematically elaborate the interaction between m6A modification and regulatory ncRNAs in function and mechanism. Moreover, we discussed the potential applications in clinical.

As one of the most common forms of RNA modification, N6-methyladenosine (m6A) RNA modification has attracted increasing research interest in recent years. This reversible RNA modification added a new dimension to the post-transcriptional regulation of gene expression. In colorectal cancer (CRC), the role of m6A modification has been extensively studied, not only on mRNAs but also on non-coding RNAs (ncRNAs). In the present review, we depicted the role of m6A modification in CRC, systematically elaborate the interaction between m6A modification and regulatory ncRNAs in function and mechanism. Moreover, we discussed the potential applications in clinical.

目的 探讨原花青素对淀粉样蛋白片段Aβ 25-35诱导的SH-SY5Y细胞JNK蛋白磷酸化水平及淀粉样蛋白Aβ 1-42和可溶性淀粉样蛋白sAPPα分泌水平的影响.方法 以1.0μ mol/L Aβ 25-35染毒SH-SY5Y细胞建立细胞损伤模型.原花青素干预24h,用MTT法检测细胞活力,ELISA法检测细胞分泌Aβ 1-42水平及sAPPα水平,Western blot法检测原花青素对SH-SYSY细胞JNK蛋白磷酸化水平的影响.结果 与1.0μmol/L Aβ 25-35染毒组相比,不同浓度原花青素可提高细胞活力,降低Aβ 1-42分泌水平及增高sAPPα分泌水平.Aβ 25-35染毒细胞可诱导p-JNK表达水平升高,给予原花青素和SP600125干预均对Aβ 25-35诱导的p-JNK表达水平升高具有抑制作用,同时降低Aβ 1-42及及增高sAPPα表达水平.结论 原花青素可以通过抑制Aβ 1-42分泌,促进sAPPα分泌,减轻神经元的Aβ负荷,其可能通过抑制JNK通道的激活发挥调节Aβ 1-42与sAPPα分泌水平的作用.