m6A-related lncRNA-based immune infiltration characteristic analysis and prognostic model for colonic adenocarcinoma

Abstract

Background Colonic adenocarcinoma (COAD) is a common gastrointestinal tract tumor, and its occurrence and progression are typically associated with genomic instability, tumor-suppressor gene and oncogene mutations, and tumor mutational load. N6-methyladenosine (m6A) modification of RNAs and long non-coding RNA (lncRNA) expression are important in tumorigenesis and progression. However, the regulatory roles of m6A‐associated lncRNAs in the tumor microenvironment, stratification of prognosis, and immunotherapy are unclear. Methods We screened 43 prognostic lncRNAs linked to m6A and performed consistent molecular typing of COAD using consensus clustering. The single-sample Gene Set Enrichment Analysis and ESTIMATE algorithms were used to assess the immune characteristics of different subgroups. Covariation between methylation-related prognostic lncRNAs was eliminated by least absolute shrinkage and selection operator Cox regression. A nomogram was created and evaluated by combining the methylation-related prognostic lncRNA model with other clinical factors. The relationship between the prognostic model grouping and microsatellite instability, immunophenotype score, and tumor mutation burden was validated using R scripts. Finally, we used a linkage map to filter sensitive medicines to suppress the expression of high-risk genes. Three m6A-associated lncRNA modes were identified in 446 COAD specimens with different clinical endpoints and biological statuses. Risk scores were constructed based on the m6A-associated lncRNA signature genes. Patients with lower risk scores showed superior immunotherapy responses and clinical benefits compared to those with higher risk scores. Lower risk scores were also correlated with higher immunophenotype scores, tumor mutation burden, and mutation rates in significantly mutated genes (e.g., FAT4 and MUC16). Piperidolate, quinostatin, and mecamylamin were screened for their abilities to suppress the expression of high-risk genes in the model. Conclusions Quantitative assessment of m6A-associated lncRNAs in single tumors can enhance the understanding of tumor microenvironment profiles. The prognostic model constructed using m6A-associated lncRNAs may facilitate prognosis and immunotherapy stratification of patients with COAD; finally, three drugs with potential therapeutic value were screened based on the model.

LncRNA WAC-AS1 promotes osteosarcoma metastasis and stemness by sponging miR-5047 to upregulate SOX2

“…SOX2 plays a critical role in maintaining the self-renewal and stemness of CSCs [11], thus we further hypothesized that WAC-AS1 promotes malignancy and stemness in OS via SOX2. We transfected the SOX2 plasmid in control or WAC-AS1-knockdown OS cells and veri ed the transfection e ciency by qRT-PCR and western blotting (Fig.…”

“…The biological function of WAC-AS1 in cancer has been reported in a limited number of papers. Based on analysis of cohorts in TCGA, WAC-AS1 regulates immune responses, immune cell in ltration, and malignant properties in various types of cancers [11]. WAC-AS1 expression also correlates with the survival of ovarian cancer patients [12].…”