背景:流行病学研究表明肺癌与结核病之间存在因果关系,尤其患有结核病的患者往往更容易患上肺腺癌,但其中的作用机制尚不清楚。前期研究发现,肺结核患者中EGFR突变和FHIT甲基化水平较高,本研究旨在查明肺腺癌和结核病患者中EGFR突变和FHIT甲基化的遗传相关性。方法:在肺腺癌和肺结核患者中,分析了表皮生长因子受体(EGFR)突变及FHIT基因的甲基化状态,并检查了结核病状态与遗传/表观遗传变异之间的关系。结果:结核患病状态与EGFR突变频率有很强的相关性,而结核患病状态与FHIT甲基化之间的关系较弱。EGFR突变与FHIT甲基化之间呈反相关关系。结论:结核病可能在增加FHIT甲基化率的同时会阻碍EGFR突变,导致患结核病后发展肺腺癌的患者对EGFR抑制剂治疗疗效不佳。Background: Epidemiological studies have shown a causal relationship between lung cancer and tuberculosis, especially in patients with tuberculosis, who are more likely to develop lung adenocar-cinoma, but the mechanism of action is not clear. Previous studies have found that EGFR mutation and FHIT methylation levels are higher in pulmonary tuberculosis patients, and this study aims to identify the genetic association of EGFR mutation and FHIT methylation in lung adenocarcinoma and tuberculosis patients. Methods: In patients with lung adenocarcinoma and tuberculosis, epidermal growth factor receptor (EGFR) mutations and methylation status of FHIT gene were analyzed, and the relationship between tuberculosis status and genetic/epigenetic variants was examined. Results: There was a strong correlation between tuberculosis prevalence and EGFR mutation frequency, while the relationship between tuberculosis prevalence and FHIT methylation was weak. There was an inverse correlation between EGFR mutations and FHIT methylation. Conclusion: Tuberculosis may hinder EGFR mutations while increasing the methylation rate of FHIT, resulting in poor response to EGFR inh
Objective:To investigate the genetic correlations between epithelial growth factor receptor(EGFR)mutation and FHIT methylation in patients diagnosed with lung adenocarcinoma(AC)and pulmonary tuberculosis(TB).Methods:The presence of EGFR mutations and the methylation status of the FHIT gene in patients presenting with AC and TB were analyzed.The correlation between TB status and the observed genetic and epigenetic variations was also examined.Results:Among the 90 patients included in the study,38 exhibited EGFR mutations(14 among those with TB and 24 among those without TB),while 29 exhibited FHIT myelination(19 among those with TB and 10 among those without TB).Furthermore,the protein expression levels of EGFR and FHIT were significantly higher in patients diagnosed solely with AC compared to those presenting with both AC and TB.A robust inverse correlation was identified between TB status and the frequency of EGFR mutation(P<0.001).Moreover,significant associations were observed between TB status and FHIT methylation(P<0.01).Conclusion:The findings suggest a correlation between TB and the prevalence of EGFR mutation and FHIT methylation in the pathogenesis of AC.
Effective treatments for neuropathic pain are lacking due to our limited understanding of the mechanisms.The circRNAs are mainly enriched in the central nervous system.However,their function in various physiological and pathological conditions have yet to be determined.Here,we identified circFhit,an exon-intron circRNA expressed in GABAergic neurons,which reduced the inhibitory synaptic transmission in the spinal dorsal horn to mediate spared nerve injury-induced neuropathic pain.Moreover,we found that circFhit decreased the expression of GAD65 and induced hyperexcitation in NK1R^(+) neurons by promoting the expression of its parental gene Fhit in cis.Mechanistically,circFhit was directly bound to the intronic region of Fhit,and formed a circFhit/HNRNPK complex to promote Pol II phosphorylation and H2B monoubiquitination by recruiting CDK9 and RNF40 to the Fhit intron.In summary,we revealed that the exon-intron circFhit contributes to GABAergic neuron-mediated NK1R^(+) neuronal hyperexcitation and neuropathic pain via regulating Fhit in cis.
