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To clarify the function of long non-coding RNA (lncRNA) GALNT5 uaRNA in cisplatin resistant colorectal cancer and its potential mechanism. The expression levels were also detected in cisplatin resistant colorectal cancer cell lines (HCT116/DDP and HT29/DDP cells) and sensitive colorectal cancer cell lines. The effects of GALNT5 uaRNA on apoptosis of HCT116/DDP and HT29/DDP cells were examined by flow cytometry assay respectively. The protein levels of drug resistance related genes influenced by GALNT5 uaRNA were detected by Western blot. The cells of siNC, sIGALNT5 uaRNA, Vector and GALNT5 uaRNA cells groups from HCT116/DDP and HT29/DDP cells were injected into dorsal flanks of the mice repectively. Higher GALNT5 uaRNA expression was observed in HCT116/DDP and HT29/DDP cells relative to that of their parental cells. The apoptotic rate increased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA knockdown compared to the cells with control group. Furthermore, the expression levels of MDR1, MRP1 and p-NF-κB were decreased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA knockdown compared to the cells with control group. The apoptotic rate decreased in HCT116/DDP and HT29/DDP cells with GALNT5 uaRNA overexpression. Furthermore, the expression levels of MDR1, MRP1 and p-NF-κB were increased in HCT116/DDP cells with GALNT5 uaRNA overexpression compared to the cells with control group. The tumors in the HCT116/DDP/siGANLNT5 uaRNAgroup were smaller and lighter than those in the HCT116/DDP/siNC. In a word GALNT5 uaRNA promotes cisplatin resistance by MDR1/MRP1/NF-κB pathway.

Background Specific tumour markers that are similar to the 21-gene assay in breast cancer, have yet to be identified in rectal cancer. The objective of this study is to identify a novel genetic signature in rectal cancer to help predict survival and provide clues for immunotherapy. Methods Differentially Expressed Genes were obtained from two GEO datasets of rectal cancer. By using data from TCGA and GSE133057, two cohorts of rectal cancer were applied to establish and evaluate the prognostic signature. Then, a nomogram was constructed to estimate survival predictability in both training and validation cohorts. Subsequently, we integrated the risk-score with clinicopathological features and assessed its interplay with immune cells and molecules. Finally, our study performed functional annotations, gene-targeted miRNAs, and single-cell analysis to reveal potential functions and relevant mechanisms. Results A total of 468 DEGs were identified between rectal cancer and normal tissues, and a signature consisting of 5 genes (CLIC5, ENTPD8, PACSIN3, HGD, and GNG7) was selected for further analyses in a prognostic model. According to the risk-score calculated by the model, results showed that overall survival was significantly worse in the high-risk group (P = 0.0044). The model exhibited high performance in time-dependent ROC as well as a nomogram. Notably, as an independent prognostic factor, the risk-score was associated with vascular invasion (P = 0.038). Furthermore, there was a dramatic difference in nonregulatory CD4 + and CD8 + T cells between the high and low-risk groups. Strikingly, the Heat map plot showed that genes in our model were correlated with immune inhibitors. Moreover, there was also a big difference in autophagy-, immune-, cell cycle-, infection-, and apoptosis-associated terms and pathways between high and low-risk groups by GO and KEGG enrichment. Then, hsa-miR-6887 was predicted to be a common microRNA of 5 genes, which was only correlated with GNG7 in expression. Markedly, the functional states of differentiation, apoptosis, and quiescence were highly related to the 5-gene signature in single-cell analysis. Conclusion Our results suggest that the 5-gene-based signature could serve as a novel prognostic biomarker in rectal cancer, which could be of benefit for decision-making in rectal cancer immunotherapy.