LncRNA LOC103694972 promotes fibrosis of NRK-49F cells by regulating STAT3-dependent Smad/CTGF pathway via targeting miR-29c-3p

Background: Renal fibrosis is an important process in the development of chronic kidney disease. Understanding the pathogenesis and finding effective treatments for renal fibrosis is crucial. This study aims to investigate whether a newly discovered long non-coding RNA (lncRNA) called LOC103694972 could be a potential target for treating fibrosis of NRK-49F cells. Methods: LncRNA Chip was used to identify differentially expressed lncRNAs between TGF-31-induced NRK-49F cells and normal cells. The dual-luciferase assay confirmed the binding between miR-29c-3p and signal transducer and activator of transcription (STAT3), as well as between miR29c-3p and lncRNA LOC103694972. Si-LOC103694972 and miR-29c-3p mimic were then transfected into TGF-31induced NRK-49F cells. Results: The study found that LOC103694972 was highly expressed in TGF-31-induced NRK-49F cells. These cells exhibited increased cell length and activity compared to the control group. The expression levels of Collagen I, alpha-Smooth muscle actin (alpha-SMA), and tissue inhibitor of metalloproteinase (TIMP-1) were increased, while matrix Metalloproteinase 2 (MMP2) and matrix Metalloproteinase 9 (MMP9) expression was decreased. However, transfection with si-LOC103694972 and miR-29c-3p mimics restored cell morphology and reduced cell viability. This led to a decrease in the levels of Collagen I, alpha-SMA, and TIMP-1, as well as an increase in MMP2 and MMP9 expression. Additionally, TGF-31-induced NRK-49F cells transfected with miR-29c-3p mimics activated the STAT3-Smad3/CTGF pathway. Conclusion: Based on these findings, lncRNA LOC103694972 shows promise as a target for treating renal fibrosis. It negatively regulates miR-29c-3p and activates the STAT3-Smad3/CTGF pathway.