Abstract
RNA binding motif protein 15 (RBM15) is a key regulatory factor involved in N6-methyladenosine (m6A) methylation. It has been reported that RBM15 plays an important role in the progress of laryngeal squamous cell carcinoma (LSCC), promoting LSCC migration and invasion. However, the role of RBM15 in human different cancers remains unknown. This study aims to analyze the prognostic value of RBM15, and to demonstrate the correlation between RBM15 expression and tumor immunity, as well as to provide clues for further mechanism research. The results showed that RBM15 was mutated or copy number varied in 25 types of cancer. RBM15 mRNA was abnormally up-regulated across various cancers. Survival analysis suggested high expression of RBM15 was associated with poor prognosis in many cancer types. Among these, it affected patients’ overall survival (OS) in 10 cancer types, disease-free interval (DFI) in 8 cancer types, progression-free interval (PFI) in 12 cancer types and disease-specific survival (DSS) in 7 cancer types. Importantly, in pancreatic adenocarcinoma (PAAD), overexpression of RBM15 is associated with patients’ OS, DFI, PFI, or DSS. In addition, RBM15 expression was positively correlated with immune infiltrating cells in kidney renal clear cell carcinoma (KIRC), brain lower grade glioma (LGG), and PAAD. Moreover, RBM15 expression showed a strong correlation with immune checkpoint markers in PAAD. Cell counting kit-8 (CCK-8) assay showed that knockdown of RBM15 significantly inhibited the proliferation of pancreatic cancer cells. PPI analysis showed USP10, USP24, SMG1, NRAS were closely connected with RBM15 alterations. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that many biological processes (BP), cellular components (CC), molecular functions (MF), cancer related pathways including “sister chromatid cohesion”, “peptidyl-serine phosphorylation”, “cell division”, “nucleoplasm”, “nucleus”, “protein binding”, “protein serine/threonine kinase activity”, “T cell receptor signaling pathway”, “Cell cycle” were regulated by RBM15 alterations. Taken together, pan-cancer analysis of RBM15 suggested it may be served as a prognostic biomarker and immunotherapeutic target for PAAD.
Highlights
N6-methyladenosine (m6A) methylation is the most abundant and common mRNA modification in higher eukaryotic cells (Qin et al, 2020; Zhang et al, 2020)
We found that RNA binding motif protein 15 (RBM15) is mutated and copy number varied in 25 cancer types
We found that RBM15 expression was associated with patients’ overall survival (OS) in 10 cancer types, including ACC, KICH, kidney renal clear cell carcinoma (KIRC), lower grade glioma (LGG), LIHC, pancreatic adenocarcinoma (PAAD), READ, STAD, THCA and THYM (Figure 3A).In addition, Kaplan-Meier OS curves showed that increased RBM15 expression was correlated with poor prognosis in 6 cancer types including ACC
Summary
N6-methyladenosine (m6A) methylation is the most abundant and common mRNA modification in higher eukaryotic cells (Qin et al, 2020; Zhang et al, 2020). RBM15, as an m6A methyltransferase, is a key regulator in RNA m6A methylation (Jiang et al, 2021). It is involved in transcriptional inhibition mediated by XIST RNA (Patil et al, 2016; Brockdorff et al, 2020). It functions as an mRNA export factor, stimulating export and expression of RTE-containing mRNAs (Lindtner et al, 2006; Zolotukhin et al, 2009). Study has shown that RBM15 promoted the progression of laryngeal squamous cell carcinoma (LSCC) by mediating the m6A modification of TMBIM6 mRNA (Wang et al, 2021). The role of RBM15 in LSCC is well understood, it’s functions in human pan-cancer remains largely unknown
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