Identification of PANoptosis-related lncRNAs in colorectal cancer: Bioinformatic and experimental insights into LMNTD2-AS1, ASMTL-AS1 and SNHG12.

Abstract

PANoptosis is a newly discovered form of programmed cell death. Accumulating studies confirmed that long non-coding RNAs (lncRNAs) play crucial role in colorectal cancer (CRC) progression. However, the role of PANoptosis-related lncRNAs in CRC has not yet been elucidated. In the current study, we used a bioinformatics pipeline to find important lncRNAs in CRC. Based on the results of in silico step, we selected RNF31, and three related lncRNAs, namely SNHG12, ASMTL-AS1 and LMNTD2-AS1 to assess their expression in 45 paired CRC and adjacent non-tumor samples. Compared with matched ANT samples, ASMTL-AS1 and SNHG12 were markedly upregulated in tumor tissues (mean fold-change 7.53, 95% CI 1.64-34.53, P = 0.009; and 8.66, 95% CI 3.15-23.78, P < 0.0001, respectively), whereas LMNTD2-AS1 was strongly downregulated (mean fold-change 0.06, 95% CI 0.014-0.26, P = 0.0004), corresponding to an approximately 16-fold reduction in tumor tissues. RNF31 showed a non-significant increase (mean fold-change 2.77, 95% CI 0.77-9.97, P = 0.15). Multivariate logistic regression incorporating all four transcripts (RNF31, ASMTL-AS1, LMNTD2-AS1, and SNHG12) demonstrated promising diagnostic performance with an AUC of 0.88 (95% CI: 0.80-0.95, P < 0.0001). These results inspire further experiments to clarify underlying mechanisms and translational studies to assess potential of mentioned lncRNAs as biomarkers.