m6A‐related long noncoding RNAs predict prognosis and indicate therapeutic response in endometrial carcinoma

Abstract

Background N6‐methyladenosine (m6A) has been identified as the most common, abundant, and conserved internal transcriptional modification. Long noncoding RNAs (lncRNAs) are noncoding RNAs consisting of more than 200 nucleotides, and the expression of various lncRNAs may affect cancer prognosis. The impact of m6A‐associated lncRNAs on uterine corpus endometrial carcinoma (UCEC) prognosis is unknown. Methods In this study, UCEC prognosis‐related m6A lncRNAs were screened, bioinformatics analysis was performed, and experimental validation was conducted. Endometrial carcinoma (EC) and normal tissue samples were obtained from The Cancer Genome Atlas. The prognosis‐related m6A lncRNAs screened by the least absolute shrinkage and selection operator method were used for multivariate Cox proportional risk regression modeling. Principal component analysis and Gene Ontology, immune function difference, and drug sensitivity analyses of the prognostic models were performed. Prognostic analysis was conducted for m6A‐associated lncRNAs. The immune infiltration relationship of m6A‐associated lncRNAs in EC was identified using the ssGSEA immune infiltration algorithm. A competing endogenouse RNA network was constructed using the LncACTdb database. Finally, quantitative real‐time polymerase chain reaction (qRT‐PCR) assays were used to validate the differences in m6A‐related lncRNA expression in normal and EC cells. Results CDKN2B‐AS1 and MIR924HG were found to be risk factors for EC. RAB11B‐AS1 was a protective factor in EC patients. MIR924HG expression was upregulated in KLE and RL95‐2 endometrial cancer cell lines. Prognostic models involved RAB11B‐AS1, LINC01812, HM13‐IT1, TPM1‐AS, SLC16A1‐AS1, LINC01936, and CDKN2B‐AS1. The high‐risk group was more sensitive to five compounds (ABT.263, ABT.888, AP.24534, ATRA, and AZD.0530) than the low‐risk group. Conclusion These findings contribute to understanding of the function of m6A‐related lncRNAs in UCEC and provide promising therapeutic strategies for UCEC.

Shining a spotlight on m6A and the vital role of RNA modification in endometrial cancer: a review

“…These mRNAs regulated cell cycle progression accompanied by immune cell infiltration, which might lead to UCEC progression ( Zhao et al, 2022 ). Likewise, the findings indicated that the constituents of hazard models relying on the lncRNAs associated with m5C, m7G, or m6A could function as significant intermediaries of the immune milieu and promising prognosis biomarkers with therapeutic response in UCEC ( Gu et al, 2022 ; Sun et al, 2022 ; Chen et al, 2023 ; Zhou et al, 2023 ). Wang et al outline new insights into CNVs/SNVs in m6A regulatory genes which were associated with a negative impact on patient survival of EC and ultimately found that three genes, IGF2BP3, KIAA1429, and IGF2BP1 , were effective predictors of EC outcomes ( Wang et al, 2020 ).…”

Biological roles of SLC16A1-AS1 lncRNA and its clinical impacts in tumors

“…In endometrial and cervical squamous cell carcinoma, SLC16A1-AS1’s upregulation and downregulation respectively are associated with overall survival [ 103 , 143 ], suggesting its role in prognostication in these cancers. Furthermore, in NSCLC [ 108 ], downregulation of SLC16A1-AS1 is linked to patient demographics, disease progression, and survival outcomes, highlighting its prognostic significance.…”