Differential expression of Nickel nanoparticles of Lactobacillus plantarum on VDR/LncRNA EIF3J-DT in Colorectal Cancer

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. VDR gene mutations and Vitamin D deficiency contribute to CRC development and progression. Certain long non-coding RNAs (lncRNAs) directly inhibit VDR gene transcription, leading to VDR mutation. Thus, targeting oncogenic lncRNAs and VDR expression is a promising strategy for effective cancer treatment. Here, we green-synthesized L. plantarum-loaded nickel nanoparticles (LpNiONPs) to assess their anticancer potential in CRC by targeting lncRNA EIF3J-DT and VDR. The bioactive component in L. plantarum was identified via GC-MS analysis, and its interaction with VDR, as well as the functional interaction with lncRNA EIF3J-DT, were evaluated using the PyRx program and RPISeq-software, respectively. The LpNiONPs were characterized using UV-Vis spectroscopy, Zeta Potential, DLS, FTIR, SEM & EDX techniques. The anticancer potential of LpNiONPs against HT-29 cells was assessed through MTT assay, scratch assay, DAPI/AO-EtBr staining, and RT-PCR to evaluate the expression of lncRNA EIF3J-DT/VDR and apoptotic-related genes. The bioactive compound Pyrrolo(1,2-a) pyrazine-1,4-dione in L. plantarum strongly interacts with VDR, highlighting its drug design potential. The formation of LpNiONPs was confirmed via UV-Vis spectroscopy with an absorption peak at 394nm. LpNiONPs were positively charged, monodispersed, and stable square-shaped nanoparticles. LpNiONPs show dose-dependent cytotoxicity and induced apoptosis, confirmed by staining images in HT-29 cells. Moreover, LpNiONPs downregulated lncRNA EIF3J-DT, CYP24-A1 and BCL2 genes while upregulating VDR, cas-3, cas-9 and BAX in HT-29 cells. These findings suggest that LpNiONPs exhibit anticancer activity by promoting VDR-associated apoptosis by inhibiting lncRNA EIF3J-DT in CRC cells.