LINCRNA01094 Promotes Renal Interstitial Fibrosis via the Mir-513b-5p/ MELK/Smad3 Axis

Area of Science:

• Genomics and Molecular Biology
• Nephrology
• Biochemistry

Background:

• Chronic Kidney Disease (CKD) poses a significant global health threat.
• Long noncoding RNAs (lncRNAs) are implicated in various diseases, acting as competing endogenous RNAs (ceRNAs).
• The specific roles of lncRNA-miRNA-mRNA networks in CKD pathogenesis remain largely undefined.

Purpose of the Study:

• To investigate the lncRNA-miRNA-mRNA network in Chronic Kidney Disease (CKD).
• To identify key molecular players and their interactions in CKD development.
• To explore the functional role of identified lncRNAs in kidney fibrosis.

Main Methods:

• Differential expression analysis of lncRNAs, miRNAs, and mRNAs in CKD patient datasets (GSE66494, GSE80247).
• Construction of competing endogenous RNA (ceRNA) interaction modules to identify hub genes.
• In vitro experiments, including cell culture (HK2 cells), gene knockdown, and TGFβ1 induction to assess fibrosis.
• RNA immunoprecipitation (RIP) and dual-luciferase reporter assays to confirm molecular interactions.

Main Results:

• Identified 33 differentially expressed lncRNAs, 20 miRNAs, and 240 mRNAs in CKD.
• Constructed two significant ceRNA modules with 11 hub nodes, including lncRNAs (LINC01086, LINC01094), miRNAs (hsa-miR-197-3p, hsa-miR-513b-5p), and mRNAs (e.g., MELK).
• Confirmed LINC01094 sponges miR-513b-5p to regulate MELK expression.
• Demonstrated that LINC01094 knockdown attenuated TGFβ1-induced fibrosis in HK2 cells.

Conclusions:

• LINC01094 plays a crucial role in mediating TGFβ1-induced renal fibrosis.
• The miR-513b-5p/MELK/Smad3 signaling axis is involved in the mechanism by which LINC01094 influences fibrosis.
• Targeting LINC01094 presents a potential therapeutic strategy for mitigating renal inflammation and fibrosis in CKD.