Bao Xinlu, Zhang Cheng, Ren Zhichao, Wang Yuxiang, Zeng Linlin
Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Science, Jilin University, Changchun 130012, China.
Int J Mol Sci. 2025 Apr 12;26(8):3666. doi: 10.3390/ijms26083666.
It has been reported that miR-375-3p plays a critical role in numerous diseases. To elucidate its biological function, particularly its differential expression and specific mechanisms of action in Alzheimer's disease (AD) and small cell lung cancer (SCLC), this study comprehensively explores the associations between the target genes of miR-375-3p and both AD and SCLC. The focus is specifically on its impact on disease progression and the remodeling of the tumor microenvironment. We utilized databases such as the miRNA TargetScanHuman 8.0 database and the STRING database, to construct a protein-protein interaction (PPI) network for the classification and discrimination of the miR-375-3p gene, resulting in the identification of 14 intersecting target genes. Subsequently, two key genes, ASCL1 and CHD7, along with their associated genes, were further analyzed using Spearman correlation analysis. The identified key genes were then subjected to GO function annotation and KEGG pathway enrichment analysis. It was determined that pathways related to lipid metabolism, autophagy, and cell apoptosis were differentially expressed in the AD and SCLC environments, with nine related pathways identified, among which the PI3K pathway was the most prominent. Finally, we demonstrated that the expression of miR-375-3p significantly differed between the two environments, with higher expression levels observed in AD compared to SCLC. Our study confirmed that miR-375-3p can promote apoptosis, regulate lipid metabolism, influence the progression of neurodegenerative diseases, and inhibit the proliferation and metastasis of tumor cells. These research findings may have significant implications for the future treatment of AD and SCLC.
据报道，miR-375-3p在多种疾病中发挥关键作用。为阐明其生物学功能，特别是其在阿尔茨海默病（AD）和小细胞肺癌（SCLC）中的差异表达及具体作用机制，本研究全面探讨了miR-375-3p的靶基因与AD和SCLC之间的关联。重点特别关注其对疾病进展和肿瘤微环境重塑的影响。我们利用miRNA TargetScanHuman 8.0数据库和STRING数据库等，构建了用于miR-375-3p基因分类和鉴别的蛋白质-蛋白质相互作用（PPI）网络，鉴定出14个交叉靶基因。随后，使用Spearman相关性分析进一步分析了两个关键基因ASCL1和CHD7及其相关基因。然后对鉴定出的关键基因进行GO功能注释和KEGG通路富集分析。结果确定，与脂质代谢、自噬和细胞凋亡相关的通路在AD和SCLC环境中存在差异表达，共鉴定出9条相关通路，其中PI3K通路最为突出。最后，我们证明miR-375-3p在两种环境中的表达存在显著差异，与SCLC相比，AD中的表达水平更高。我们的研究证实，miR-375-3p可促进细胞凋亡、调节脂质代谢、影响神经退行性疾病的进展并抑制肿瘤细胞的增殖和转移。这些研究结果可能对AD和SCLC的未来治疗具有重要意义。
