m6A RNA methylation regulators were associated with the malignancy and prognosis of ovarian cancer

Abstract

N6-methyladenosine (m6A) RNA methylation regulators play a regulatory role in tumor pathogenesis and development. However, the role of m6A regulator genes in ovarian cancer (OC) has not been fully elucidated. This study aims to investigate the mRNA expressions, clinicopathological features, and prognostic values of m6A regulators in OC. Here, we demonstrate that the 17 m6A RNA methylation regulators are differentially expressed in ovarian cancer and normal tissues. By using consensus clustering, all ovarian cancer patients can be divided into two subgroups (cluster 1 and 2) based on the expression of 17 m6A RNA methylation regulators. Using Gene Set Enrichment Analysis, we identified that cluster 1 was most connected to oxidative phosphorylation pathways. Regression models identified that prognosis is associated with HNRNPA2B1, KIAA1429, and WTAP. qRT-PCR result show that the expression trends of HNRNPA2B1 and KIAA1429 are consistent with the predicted results. Multivariate Cox regression analysis results show that the risk score was an independent predictive factor in OV. The overall survival of highrisk patients was significantly shorter than that of low-risk patients. ROC curve analysis showed that the prognostic signature precisely predicted the 5-year survival of OV patients. A nomogram was developed to predict each patient's survival probability and well calibrated and showed a satisfactory discrimination. Dendritic fraction, macrophage fraction, and neutrophil fraction showed higher fraction in high-risk patients. In conclusion, m6A RNA methylation regulators are vital participants in ovarian cancer pathology, and three-gene mRNA levels are valuable factors for prognosis predictions.

RETRACTED ARTICLE: Long noncoding RNA UBA6-AS1 inhibits the malignancy of ovarian cancer cells via suppressing the decay of UBA6 mRNA

“…For example, KIAA1429-induced m 6 A promoted the translation of c-MYC, BCL2, and Phosphatase and tensin homolog (PTEN) mRNAs in the human acute myelocytic leukemia (AML) cells, suppressing the differentiation and apoptosis of AML cells [ 8 ]. In OC, KIAA1429 and METTL3 is associated with the prognosis of OC patients [ 9 , 10 ]. METTL3 promotes OC growth and invasion through the regulation of AXL receptor tyrosine kinase (AXL) translation and epithelial to mesenchymal transition (EMT) [ 9 ].…”

Emerging Roles of m6A RNA Methylation Regulators in Gynecological Cancer

“…IGF2BP3, KIAA1429, IGF2BP1, YTHDF3, ZC3H13, YTHDC1, and METTL14 can be used as prognostic markers of endometrial cancer (93,94). HNRNPA2B1, KIAA1429, and WTAP can be used as prognostic markers of ovarian cancer (114). However, these studies are based only on systematic analyses of public databases.…”

“…Bioinformatics and Cox multivariate analysis showed the significant correlation between high expression of WTAP and ovarian cancer prognosis(113). Meanwhile, analysis of other gene sets found that the prognosis of ovarian cancer was associated with HNRNPA2B1, KIAA1429, and WTAP(114). Na et al identified NEBL, PDGFRA, WDR91, and ZBTB4 genes as potential independent prognostic risk characteristics of ovarian cancer(115).…”

N6-methyladenosine (m6A)-mediated up-regulation of long noncoding RNA LINC01320 promotes the proliferation, migration, and invasion of gastric cancer via miR495-5p/RAB19 axis

“…The methyltransferase catalyzes the production of m6A in the form of complexes in the nucleus. The complex consists of an interacting protein, such as METTL14 and WTAP [ 36 ]. These proteins modulate m6A modification in non-coding RNAs.…”