Nephrology (Carlton, Vic.) · 2025
Long non-coding RNA Growth Arrest Specific 5 Regulates the Podocyte Function in Nephrotic Syndrome Development via microRNA-144-5p/Phosphatase And Tensin Homolog.
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Zhang Xinyi, Tian Huan, Lu Chang, Xie Shen-Ping, Ma Jing-Sheng, Chen Huai-Zhou, Tang Dong-E, Dai Yong, Yan Qiang, Xian Wei
Аннотация
AIM: This research examined the role and possible regulatory mechanisms of lncRNA GAS5 in the occurrence and progression of primary nephrotic syndrome (PNS) to provide biomarkers for early screening of PNS in the clinic.
METHODS: RT-qPCR was employed to assess the expression levels of GAS5 and miR-144-5p. ROC analysis was conducted to evaluate their predictive capabilities for PNS. The interaction between GAS5 and miR-144-5p was confirmed using a dual-luciferase assay. Following this, GAS5 overexpression plasmids, along with co-transfected plasmids, were introduced into podocytes to examine their impact on the inflammatory factors, oxidative stress index, cell proliferation and apoptosis. Furthermore, we performed GO and KEGG enrichment analyses, along with PPI analysis, on the target genes of miR-144-5p to speculate on its potential functions and to identify critical genes.
RESULTS: The expression levels of GAS5 were decreased while miR-144-5p levels were elevated in PNS patients. The diagnostic approach of serum GAS5 combined with miR-144-5p improved the accuracy of identification. GAS5 was observed to inhibit inflammation and oxidative stress responses and the apoptosis of MPC-5 cells, and enhance cell proliferation. However, the overexpression of miR-144-5p counteracted the effect of GAS5 on podocyte function. Enrichment analysis suggested the miR-144-5p target genes could affect podocyte structure, homeostasis and cell growth. PTEN and STAT3 are identified as critical regulatory targets.
CONCLUSION: The sponging effect of GAS5 on miR-144-5p caused changes in PTEN mRNA expression and could potentially prevent or mitigate PNS. GAS5 is expected to become a potential target for treating PNS.
METHODS: RT-qPCR was employed to assess the expression levels of GAS5 and miR-144-5p. ROC analysis was conducted to evaluate their predictive capabilities for PNS. The interaction between GAS5 and miR-144-5p was confirmed using a dual-luciferase assay. Following this, GAS5 overexpression plasmids, along with co-transfected plasmids, were introduced into podocytes to examine their impact on the inflammatory factors, oxidative stress index, cell proliferation and apoptosis. Furthermore, we performed GO and KEGG enrichment analyses, along with PPI analysis, on the target genes of miR-144-5p to speculate on its potential functions and to identify critical genes.
RESULTS: The expression levels of GAS5 were decreased while miR-144-5p levels were elevated in PNS patients. The diagnostic approach of serum GAS5 combined with miR-144-5p improved the accuracy of identification. GAS5 was observed to inhibit inflammation and oxidative stress responses and the apoptosis of MPC-5 cells, and enhance cell proliferation. However, the overexpression of miR-144-5p counteracted the effect of GAS5 on podocyte function. Enrichment analysis suggested the miR-144-5p target genes could affect podocyte structure, homeostasis and cell growth. PTEN and STAT3 are identified as critical regulatory targets.
CONCLUSION: The sponging effect of GAS5 on miR-144-5p caused changes in PTEN mRNA expression and could potentially prevent or mitigate PNS. GAS5 is expected to become a potential target for treating PNS.