Identification of ALYREF in pan cancer as a novel cancer prognostic biomarker and potential regulatory mechanism in gastric cancer

Sep 21, 2026

Uploaded by Finn

ALYREF, an mRNA m5C-binding protein involved in RNA export and transcriptional regulation, is analyzed across pan-cancer cohorts to clarify its role in carcinogenesis and clinical outcome. TCGA and GTEx datasets show ALYREF is broadly upregulated and elevated levels associate with poor prognosis in multiple cancers. Functional enrichment indicates ALYREF regulates the cell cycle and gene mismatch repair during tumor progression. In stomach adenocarcinoma, ALYREF correlates with tumor stemness, and gastric subtype-specific analyses link high expression to worse outcomes. siRNA knockdown in AGS cells suppresses proliferation, induces G1 arrest, and increases apoptosis, supporting ALYREF as a prognostic biomarker and therapeutic target.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Results

Differential expression profiles of ALYREF and correlation with prognosis in pan-cancer

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Identification of ALYREF in pan cancer as a novel cancer prognostic biomarker and potential regulatory mechanism in gastric cancer Yujie Yuan1,4, Yiyang Fan2,4, Wenqing Tang3, Hui Sun3, Jinghan Sun3, Hongmeng Su1 & Hong Fan1* ALYREF is considered as a specific mRNA m5C-binding protein which recognizes m5C sites in RNA and facilitates the export of RNA from the nucleus to the cytoplasm. Expressed in various tissues and highly involved in the transcriptional regulation, ALYREF has the potential to become a novel diagnostic marker and therapeutic target for cancer patients. However, few studies focused on its function during carcinogenesis and progress. In order to explore the role ofALYREF on tumorigenesis, TCGA and GTEx databases were used to investigate the relationship of ALYREF to pan-cancer. We found that ALYREF was highly expressed in majority of cancer types and that elevated expression level was positively associated with poor prognosis in many cancers. GO and KEGG analysis showed that ALYREF to be essential in regulating the cell cycle and gene mismatch repair in tumor progression. The correlation analysis of tumor heterogeneity indicated that ALYREF could be specially correlated to the tumor stemness in stomach adenocarcinoma (STAD). Furthermore, we investigate the potential function of ALYREF on gastric carcinogenesis. Prognostic analysis of different molecular subtypes of gastric cancer (GC) unfolded that high ALYREF expression leads to poor prognosis in certain subtypes of GC. Finally, enrichment analysis revealed that ALYREF-related genes possess the function of regulating cell cycle and apoptosis that cause further influences in GC tumor progression. For further verification, we knocked down the expression of ALYREF by siRNA inGC cell line AGS. Knockdown of ALYREF distinctly contributed to inhibition of GC cell proliferation. Moreover, it is observed that knocked-down of ALYREF induced AGS cells arrested inG1 phase and increased cell apoptosis. Our findings highlighted the essential function of ALYREF in tumorigenesis and revealed the specific contribution of ALYREF to gastric carcinogenesis through pan-cancer analysis and biological experiments. Cancer remains the world’s leading cause of death with increased morbidity and mortality, although the clinical treatments including surgery operation, chemotherapy, radiotherapy, immunotherapy have improved the survival outcome of tumor patients1. Therefore, there is an urgent need for a novel diagnostic marker and therapeutic target molecule for cancer patients. In the past few years, extended studies in RNA biology have disclosed RNA methylation involved in carcinogenesis by promoting regulatory RNA function2–4. Increasing evidence supported that 5-methylcytosine in RNA is associated with multifarious cellular processes during tumorigenesis, such as cell proliferation, cell migration and tumor progression5. In m5C-dependent regulation, writer NOP2/Sun RNA Methyltransferase 2 (NSUN2) plays crucial roles in tumor progression6,7, Aly/REF export factor (ALYREF) considered as a reader of mRNA m5C facilitates the export of RNA from the nucleus to the cytoplasm8,9. ALYREF, localized on chromosome band 17q25.3 and functions as a molecular chaperone, is involved in the transcriptional regulation10, 11. ALYREF is expressed in the esophagus, kidney, stomach, liver, lung, colon, thyroid, and 20 other tissues12. To be of interest, ALYREF was involved in transcription elongation, genome stability13, 14, RNA export from nucleus, and mRNA processing9. More and more evidence testified that ALYREF plays an 1The Key Laboratory of Developmental Genes and Human Diseases, Department of Medical Genetics and Developmental Biology, School of Medicine, Ministry of Education, Southeast University, Nanjing 210009, China. 2Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill,

FAQs

What is ALYREF and why is it relevant to cancer biology?

ALYREF is an mRNA m5C-binding protein that recognizes m5C sites and promotes RNA export from the nucleus to the cytoplasm. It is also implicated in transcriptional regulation, making it a candidate diagnostic and therapeutic molecule in cancer.

How does ALYREF expression relate to prognosis across cancers?

Across TCGA and GTEx-based analyses of 32 cancer types, ALYREF is significantly increased in most tumors compared with normal tissues. Higher ALYREF expression is positively associated with poor prognosis in many cancers.

What experimental evidence supports ALYREF’s role in gastric cancer?

In AGS gastric cancer cells, siRNA-mediated ALYREF knockdown reduces cell proliferation and foci formation. Knockdown also causes G1 phase cell cycle arrest and increases cell apoptosis, consistent with a pro-carcinogenic function.

Sep 21, 2026

Uploaded by Finn