Mechanistic Insights into Gemini-Cur Enhanced Therapeutic Efficacy in Colorectal Cancer: The Role of Differentially Expressed lncRNAs

Due to the high incidence and rapid progression of colorectal cancer, many patients are deprived of the option of cure or surgical resection and some of them are diagnosed at a late stage due to the absence of obvious symptoms. Although surgical resection improves patient survival and other adjuvant therapies improve prognosis, CRC patients usually have a poorer prognosis and more side effects. so the search for drugs with good anticancer effects and reduced side effects has become a new research goal and hot spot. Based on the therapeutic characteristics of Chinese medicine as “multi-component, multi-target, and multi-pathway”, Curcumin has also been extensively used in the research and treatment of cancers, but the molecular mechanisms and metabolic pathways of this compound in colorectal cancer remain not fully elucidated. Therefore, this paper aims to reveal the possible novel targets of Gemini-Cur on colorectal cancer and related cellular pathways through lncRNA expression profile and bioinformatics, so as to make a modest contribution to the treatment of CRC by curcumin. In the present study, RNAs from colorectal cancer cells with and without gemini-curcumin treatment were sequenced, quantified, and normalized. Consequently, ۳۴۷ DElncRNAs (padj < ۰.۰۱, log۲ FC ≥ ۲) were identified and for doing the downstream analysis, Top-۲۰-lncRNAs, from DelncRNAs, were selected. Notably, Gemini-cur treatment upregulated tumor-suppressive lncRNAs such as C۸orf۳۱ and ARHGAP۵-AS۱, while downregulating oncogenic lncRNAs including XIST, FTX, and NEAT۱. to determine the potential functions of Top-۲۰-lncRNAs differentially expressed in treated colorectal cancer cells, the functions of their target genes were analyzed. GO and KEGG pathway analysis revealed that the target genes are involved in certain pathways associated with cancer, such as cell cycle, p۵۳ signaling pathways, translation and helicase activity. Finally to validate our results, we used TCGA database through online tools to Evaluation of expression, promoter Methylation, survival and mutational statement of selected genes. This study provides novel insights into the molecular mechanisms through which Gemini-cur modulates lncRNA expression and presents potential targets for therapeutic intervention in CRC. Future research is warranted to further validate these findings and explore the therapeutic implications of lncRNA-targeted strategies.

کلیدواژه ها:

Colorectal cancer ، Gemini-cur ، lncRNA