PGM1 and ENO1 Promote the Malignant Progression of Bladder Cancer via Comprehensive Analysis of the m6A Signature and Tumor Immune Infiltration

Abstract

Background. While N6-methyladenosine (m6A) modification of RNA and the tumor immune microenvironment both influence the progression of cancer, little attention has been paid to interactions between these two factors. Thus, we systematically explored potential biomarkers in the malignant progression of bladder urothelial carcinoma (BLCA) via combining expression of m6A methylation regulators with tumor immune infiltration. Methods. We extracted m6A regulators from published literature, downloaded BLCA RNA-seq and clinical information from the Cancer Genome Atlas database, and integrated three main bioinformatic methods and qPCR to explore the biological variations in the malignant progression of BLCA. Results. FTO, IGF2BP3, and YTHDC1 have a significant difference in bladder cancer and prognosis. Two subgroups (clusters 1 and 2) were identified according to three key m6A regulators; cluster 1 was preferentially associated with poor prognosis and immune infiltration relative to cluster 2 significantly. We further identified PGM1 and ENO1 as potential prognostic biomarkers, as they were correlated with FTO and IGF2BP3 positively but with YTHDC1, negatively. M2 macrophage and TFH cells were highly infiltrated in BLCA and were associated with BLCA prognosis. Finally, PGM1 and ENO1 were correlated with M2 macrophage and TFH cells and their surface markers CD163and CXCR5. Conclusions. PGM1 and ENO1 are highly correlated with the malignant progression of BLCA, and the expression of these genes may be new indicators for the diagnosis and prognosis of BLCA.

Four types of adenine-related RNA modification writers -mediated molecular subtypes contribute to predicting clinical outcomes and treatment options in bladder cancer

“…Increasing evidence indicate that RNA modification writers play a critical role in tumor immunity. For example, Zhao J et al (52) revealed that the elevated expression of m6A related genes including ENO1 and PGM1 was positively correlated with infiltration of M2 macrophages and their surface marker CD163, hence affecting the prognosis of BLCA patients. However, previous studies have concentrated on a single type of RNA modification writers, leaving the mutual relationships of multiple RNA modification writer types in BLCA remains unknown.…”

ENO1 expression and Erk phosphorylation in PDAC and their effects on tumor cell apoptosis in a hypoxic microenvironment

“…Numerous studies have implicated hypoxia-dependent/independent pathways and ENO1 upregulation in hypoxic therapeutic resistance 38 , 39 . Research has focused on the role of ENO1 in tumor progression and cancer treatment 40 . Our data demonstrated that knockdown of ENO1 promotes apoptosis in vitro and in vivo , and ERK pathway activation blocks this effect.…”

RNA m6Amethylation in cancer

“…10.1.2. type="main">m 6 A-related RNAs Over 138 m 6 A-related transcripts were identified to be potential prognostic biomarkers so far, such as NMPM1 in lung adenocarcinoma [255], SNRPC in HCC [256], GLUT1 in esophageal cancer [257], BATF2 in GC [258], PGM1 and ENO1 in BCA [259], NUF2/ CDCA3/KIF14 in clear cell renal cell carcinoma [260]. m 6 A-associated miRNAs are also used for developing new cancer biomarkers.…”