LncRNA RMRP participates in Nano NiO-induced collagen synthesis of BEAS-2B cells by modulating PRKCB DNA methylation-mediated ferritinophagy

Nano nickel oxide (Nano NiO) is known to contribute to the development of pulmonary fibrosis; however, the epigenetic mechanisms underlying its effects remain largely unclear. This study investigated the associations among lncRNA RMRP, PRKCB DNA methylation status, and ferritinophagy in the context of Nano NiO-stimulated collagen synthesis. Following the establishment of a Nano NiO-induced collagen synthesis model in BEAS-2B cells, protein and mRNA expression were quantified via Western blot and qPCR, respectively, while DNA methylation was determined by bisulfite sequencing PCR. Our findings demonstrated that Nano NiO exposure led to increased lncRNA RMRP expression, PRKCB DNA hypomethylation, suppressed ferritinophagy, and enhanced collagen synthesis in BEAS-2B cells. Knockdown of lncRNA RMRP, however, largely reversed these Nano NiO-induced changes. In addition, treatment with decitabine, a DNA methylation inhibitor, attenuated the upregulation of PRKCB2, suppression of ferritinophagy, and collagen synthesis triggered by Nano NiO. However, ferritinophagy and collagen synthesis were respectively controlled by overexpressing PRKCB2, silencing PRKCB2, and treating with the PRKCB2 inhibitor LY317615. Finally, NCOA4 overexpression reversed Nano NiO-induced PRKCB hypomethylation, PRKCB2 upregulation, and excessive collagen synthesis. In conclusion, lncRNA RMRP and PRKCB DNA methylation may represent potential biomarkers and therapeutic targets in pulmonary fibrosis.