m6A RNA Methylation Regulators Impact Prognosis and Tumor Microenvironment in Renal Papillary Cell Carcinoma

Abstract

Accumulating evidence has proven that N6-methyladenosine (m6A) RNA methylation plays an essential role in tumorigenesis. However, the significance of m6A RNA methylation modulators in the malignant progression of papillary renal cell carcinoma (PRCC) and their impact on prognosis has not been fully analyzed. The present research set out to explore the roles of 17 m6A RNA methylation regulators in tumor microenvironment (TME) of PRCC and identify the prognostic values of m6A RNA methylation regulators in patients afflicted by PRCC. We investigated the different expression patterns of the m6A RNA methylation regulators between PRCC tumor samples and normal tissues, and systematically explored the association of the expression patterns of these genes with TME cell-infiltrating characteristics. Additionally, we used LASSO regression to construct a risk signature based upon the m6A RNA methylation modulators. Two-gene prognostic risk model including IGF2BP3 and HNRNPC was constructed and could predict overall survival (OS) of PRCC patients from the Cancer Genome Atlas (TCGA) dataset. The prognostic signature-based risk score was identified as an independent prognostic indicator in Cox regression analysis. Moreover, we predicted the three most significant small molecule drugs that potentially inhibit PRCC. Taken together, our study revealed that m6A RNA methylation regulators might play a significant role in the initiation and progression of PRCC. The results might provide novel insight into exploration of m6A RNA modification in PRCC and provide essential guidance for therapeutic strategies.

MYC-activated RNA N6-methyladenosine reader IGF2BP3 promotes cell proliferation and metastasis in nasopharyngeal carcinoma

“…For example, Zhang et al found that IGF2BP3 is generally up-regulated in 18 TCGA tumors, and the high expression level of IGF2BP3 affects the immune microenvironment and drug sensitivity, leading to poor prognosis [ 24 ]. Simultaneously, IGF2BP3 was identified as an independent prognostic indicator in renal papillary cell carcinoma [ 25 ], hematological malignancies [ 26 ], and prostate cancer [ 27 ]. Consistent with these studies, we found that IGF2BP3 was upregulated in patients with NPC and NPC cells.…”

Effects of RNA methylation N6-methyladenosine regulators on malignant progression and prognosis of melanoma

“…These findings provide a framework for the development and usage of m6A WREs inhibitors in melanoma treatment. However, these studies focused on the m6A WREs at the level of a single gene, whereas the combination of m6A WREs with clinicopathological parameters has shown great potential in the prognosis prediction of cancers, such as hepatocellular carcinoma, lung squamous cell carcinoma, and renal papillary cell carcinoma [ 40 – 42 ].…”

“…Several evidences have displayed the involvement of m6A regulators modification in innate and adaptive immune responses [ 42 , 46 ], but its mechanism of shaping the tumor microenvironment in melanoma remains poorly understood. We have verified the oncogenic functions of IGF2BP3 in melanoma via cell functional experiments.…”

N6-Methyladenosine RNA Modification in the Tumor Immune Microenvironment: Novel Implications for Immunotherapy

“…Among patients receiving immune checkpoint therapies, the clinical benefits were significantly higher in patients with high m 6 A scores ( 119 ). The expressions of 17 m 6 A RNA methylation regulators were closely related to the immunity and malignant progression of papillary renal cell carcinoma ( 120 ).…”