Differential expression of nickel nanoparticles of Lactobacillus plantarum on VDR/LncRNA EIF3J-DT in Colorectal cancer

Abstract

Colorectal cancer (CRC) is the third most prevalent cancer worldwide. Vitamin D receptor (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 Lactobacillus plantarum loaded nickel oxide nanoparticles (LpNiONPs) to assess their anticancer potential in CRC by targeting long non-coding RNA EIF3J- divergent transcript (lncRNA EIF3J-DT) and VDR. The potent bioactive component present in L. plantarum was identified via gas chromatography-mass spectrometry (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, dynamic light scattering (DLS), fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), energy dispersive X-ray (EDX) and X-ray diffraction (XRD) techniques. The anticancer potential of LpNiONPs against HT-29 cells was assessed through 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, scratch assay, 4′,6-diamidino-2-phenylindole (DAPI)/ acridine orange-ethidium bromide (AO-EtBr) staining experiments, and reverse transcriptase-PCR to evaluate the expression of lncRNA EIF3J-DT/VDR and apoptotic-related genes. The potent 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 394 nm. 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.

Keywords

• Colorectal Cancer
• lncRNA EIF3J-DT
• VDR
• Lactobacillus plantarum
• Nickel oxide nanoparticle