Hyperproliferation of mesangial cells (MCs) is the central pathological feature observed in certain human renal diseases. Furthermore, the long non‑coding RNA uc.412 is regulated by transforming growth factor β1 in mesangial cells in vitro. The present study aimed to investigate whether uc.412 serves a role in renal fibrosis and whether it may be considered as a therapeutic target in mesangial proliferative kidney diseases. The results demonstrated that uc.412 overexpression significantly increased MC proliferation. The transcriptional profile of MCs overexpressing uc.412 was assessed by RNA sequencing. A total of 462 up‑ and 843 downregulated genes were identified (|fold change| ≥1.5), and reverse transcription‑quantitative PCR was used to determine the expression of these differentially expressed genes (DEGs). Subsequently, the potential function of these DEGs was determined by bioinformatics analyses. The results indicated that these DEGs were involved in numerous signaling pathways associated with MC proliferation. The downstream association between up‑ and downregulated genes was constructed via the STRING database. The protein‑protein interaction network indicated that serpin family E member 1 and matrix metallopeptidase 3 may be hub proteins. In conclusion, the present study provided novel insight into the role of uc.412 in MC proliferation, which may aid in the development of novel treatment for mesangial proliferative kidney diseases.