The 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.
Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Sci Rep. 2024 Mar 15;14(1):6270. doi: 10.1038/s41598-024-56895-5.
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.
ALYREF 被认为是一种特定的 mRNA m5C 结合蛋白，可识别 RNA 中的 m5C 位点，并促进 RNA 从核内输出到细胞质。ALYREF 在各种组织中表达，高度参与转录调控，有可能成为癌症患者的新型诊断标志物和治疗靶点。然而，很少有研究关注其在癌发生和进展中的功能。为了探讨 ALYREF 在肿瘤发生中的作用，我们使用 TCGA 和 GTEx 数据库研究了 ALYREF 与泛癌的关系。我们发现 ALYREF 在大多数癌症类型中高表达，并且在许多癌症中表达水平升高与预后不良呈正相关。GO 和 KEGG 分析表明，ALYREF 在肿瘤进展中对细胞周期和基因错配修复的调节至关重要。肿瘤异质性的相关性分析表明，ALYREF 可能与胃腺癌（STAD）的肿瘤干性特别相关。此外，我们研究了 ALYREF 对胃癌发生的潜在功能。不同分子亚型胃癌（GC）的预后分析表明，高 ALYREF 表达导致某些 GC 亚型预后不良。最后，富集分析表明，ALYREF 相关基因具有调节细胞周期和凋亡的功能，这进一步影响 GC 肿瘤的进展。为了进一步验证，我们通过 siRNA 在 GC 细胞系 AGS 中敲低 ALYREF 的表达。敲低 ALYREF 明显促进 GC 细胞增殖的抑制。此外，观察到敲低 ALYREF 诱导 AGS 细胞停滞在 G1 期并增加细胞凋亡。我们的研究结果强调了 ALYREF 在肿瘤发生中的重要功能，并通过泛癌分析和生物学实验揭示了 ALYREF 对胃癌发生的特定贡献。
