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

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 of ALYREF 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 in GC 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 in G1 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.