Engagement of N^(6)-methyladenisine methylation of Gng4 mRNA in astrocyte dysfunction regulated by CircHECW2

The N^(6)-methyladenosine(m^(6)A)modification is the most prevalent modification of eukaryotic mRNAs and plays a crucial role in various physiological processes by regulating the stability or function of target mRNAs.Accumulating evidence has suggested that m6A methylation may be involved in the pathological process of major depressive disorder(MDD),a common neuropsychiatric disorder with an unclear aetiology.Here,we found that the levels of the circular RNA HECW2(circHECW2)were significantly increased in the plasma of both MDD patients and the chronic unpredictable stress(CUS)mouse model.Notably,the downregulation of circHECW2 attenuated astrocyte dysfunction and depression-like behaviors induced by CUS.Furthermore,we demonstrated that the downregulation of circHECW2 increased the expression of the methylase WTAP,leading to an increase in Gng4 expression via m^(6)A modifications.Our findings provide functional insight into the correlation between circHECW2 and m^(6)A methylation,suggesting that circHECW2 may represent a potential target for MDD treatment.

GNG4下调对人结直肠癌细胞生物学行为的影响研究

本研究旨在通过体外实验降低GNG4基因表达水平,研究其对结直肠癌细胞增殖和迁移等生物学行为的影响,以期为结直肠癌的靶向治疗提供新的思路。方法 使用生物信息学和免疫组织化学染色等技术验证结直肠癌组织细胞与正常结直肠上皮组织细胞中GNG4表达水平的差异。然后,通过降低结直肠癌细胞SW620和SW948中的GNG4表达水平,利用细胞划痕、CCK-8和细胞克隆等功能实验验证降低GNG4基因表达后SW620和SW948肿瘤细胞的生物学行为变化。结果 与正常结直肠组织细胞相比,结直肠癌组织和细胞中的GNG4表达水平明显增高。在降低GNG4基因表达后,结直肠癌细胞的增殖、迁移能力和细胞集落能力均显著降低,其生物学行为受到明显影响。结论 GNG4在结直肠癌中表达水平较高,降低GNG4会显著影响结直肠癌细胞的增殖和迁移等生物学行为。这些实验结果可能为结直肠癌的基础研究和靶向治疗提供新的方向和策略。