Decreased m6A Modification of CD34/CD276(B7-H3) Leads to Immune Escape in Colon Cancer

Abstract

Previous studies have reported that m6a modification promotes tumor immune escape by affecting tumor microenvironment (TME). Due to the complexity of TME, a single biomarker is insufficient to describe the complex biological characteristics of tumor and its microenvironment. Therefore, it is more meaningful to explore a group of effective biomarkers reflecting different characteristics of cancer to evaluate the biological characteristics of solid tumors. Here, the immune gene CD34/CD276 with different m6A peak was obtained by m6A sequencing (MeRIP-seq) of colon cancer (CRC)clinical samples and combined with MsIgDB database, which was used to perform cluster analysis on TCGA-COAD level 3 data. The CD34/CD276 as a molecular marker for CRC prognosis was confirmed by survival analysis and immunohistochemical assay. Further bioinformatics analysis was carried out to analyze the molecular mechanism of CD34/CD276 affecting the TME through m6a-dependent down-regulation and ultimately promoting immune escape of CRC.

Epitranscriptic regulation of HRAS by N 6 -methyladenosine drives tumor progression

“…To explore the high m 6 A modification genes in cancer, we constructed a comprehensively differential m 6 A modification landscape across four distinct cancer types that contained 30 patient tumors and adjacent tissues from public meRIP-Seq datasets ( SI Appendix , Table S1 ) ( 13 – 16 ). We identified thousands of differential m 6 A modification genes in ovarian cancer, endometrial cancer, hepatocellular carcinoma, and colon cancer tissues compared with adjacent tissues ( Dataset S1 ), and there were only 446 overlapped genes among these cancer types ( SI Appendix , Fig.…”

Immune checkpoint of B7-H3 in cancer: from immunology to clinical immunotherapy

“…In addition to microRNA-29, more than 10 microRNAs have been demonstrated to regulate the expression of B7-H3 and influence tumor behaviors, as reviewed by Feng et al [ 9 ]. Moreover, N6-methyladenosine (m 6 A) RNA modification of B7-H3 mRNA was found to be significantly downregulated in CRC tissues compared with normal tissues, which further participated in immune escape, indicating epigenetic reprogramming’s role in B7-H3 function [ 85 ]. Altogether, B7-H3 is involved in tumor proliferation, metabolism, and invasion and a series of malignant behaviors, which confirms that B7-H3 is a valuable research object to further elucidate tumor biology and a therapeutic target to block tumor progression.…”

The importance of N6-methyladenosine modification in tumor immunity and immunotherapy

“…IL-2 receptors can be regulated by the SOCS family and activate STAT5 [ 92 ]. When METTL3 in Treg cells is depleted, it will cause the increase of SOCS gene family mRNA, thus inhibiting the IL2-STAT5 signaling pathway, and finally maintain the Treg inhibitory function [ 93 ]. Exploring the mechanism of T cell-mediated immune evasion and discovering more about its relationship with m6A modifications will facilitate immunotherapy of tumors.…”