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TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression

ABSTRACT: Background: The lack of obvious symptoms of early gastric cancer (GC) as well as the absence of sensitive and specific biomarkers results in poor clinical outcomes. Tubulin is currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders, however, its mechanism of action in gastric cancer is still unclear. Tubulin alpha-1C(TUBA1C) is a subtype of α-tubulin, high TUBA1C expression has been shown to be closely related to a poor prognosis in in various cancers,this study, for the first time, revealed the mechanism of TUBA1C promotes malignant progression of gastric cancer in vitro and in vivo. Methods: The expression of lncRNA EGFR-AS1 was detected in human GC cell lines by qRT–PCR. Mass spectrometry experiments following RNA pulldown assays found that EGFR-AS1 directly binds to TUBA1C, the CCK8, EdU, transwell, wound-healing, cell cycle assays and animal experiments were conducted to investigate the function of TUBA1C in GC. Combined with bioinformatics analyses, reveal interaction between Ki-67, E2F1, PCNA and TUBA1C by western blot. Rescue experiments furtherly demonstrated the relationship of EGFR-AS1and TUBA1C. Results: TUBA1C was proved to be a direct target of EGFR-AS1, TUBA1C promotes gastric cancer proliferation, migration and invasion by accelerating the progression of the cell cycle from the G1 phase to the S phase and activating the expression of oncogenes: Ki-67,E2F1 and PCNA. Conclusions: TUBA1C is a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression and could be a novel biomarker and therapeutic target for GC.

INSTRUMENT(S): LCQ Classic

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Stomach

SUBMITTER: lipan peng

LAB HEAD: Lipan Peng

PROVIDER: PXD040199 | Pride | 2023-05-10

REPOSITORIES: Pride

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TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression.

Wang Haodong H Cui Huaiping H Yang Xinjun X Peng Lipan L

BMC cancer 20230320 1

<h4>Background</h4>The lack of obvious symptoms of early gastric cancer (GC) as well as the absence of sensitive and specific biomarkers results in poor clinical outcomes. Tubulin is currently emerging as important regulators of the microtubule cytoskeleton and thus have a strong potential to be implicated in a number of disorders, however, its mechanism of action in gastric cancer is still unclear. Tubulin alpha-1 C (TUBA1C) is a subtype of α-tubulin, high TUBA1C expression has been shown to be ...[more]

PMID: 36941595

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Project description:METTL3-mediated RNA N6-methyladenosine (m6A) is the most prevalent modification participates in tumor initiation and progression via regulating expression of their target genes in cancers. However, its role in tumor cell metabolism remains poorly appreciated. In this study, we conducted a multi-omics analysis including m6A microarray and quantitative proteomics to explore the potential effect and mechanism of METTL3 on the metabolism in gastric cancer cells. Our results found that significant alterations in the protein and m6A modification profile which induced by METTL3 overexpression in GC cells. Gene Ontology (GO) enrichment results showed that down-regulated proteins were significantly enriched in intracellular mitochondrial oxidative phosphorylation (OXPHOS), and the Protein-Protein Interaction (PPI) network analysis found that these differentially expressed proteins were significantly associated with OXPHOS. Subsequently, a prognostic model constructed based on the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases, and the high-risk group showed a worse prognosis in GC patients. Meanwhile, the Gene Set Enrichment Analysis (GSEA) showed a significant enrichment in the energy metabolism signaling pathway. Then, combined with the results of the m6A microarray analysis, the intersection molecules of DEPs and differential methylation genes (DMGs) were significantly correlated with the genes involved in OXPHOS. Besides, there were also significant differences in prognosis and GSEA enrichment between the two clusters of GC patients classified according to consensus clustering algorithm. Finally, we focused on highly expressed, highly methylated molecules regulated by METTL3 and identified three (AVEN, DAZAP2, DNAJB1) genes that were significantly associated with poor prognosis in patients with GC. These results indicated that METTL3-regulated DEPs in GC cells were significantly associated with OXPHOS. After combined with m6A microarray analysis, the results suggested that these proteins might be involved in cell energy metabolism through m6A modifications thus influencing the prognosis of GC patients. Overall, our study revealed that METTL3 involved in cell metabolism through an m6A-dependent mechanism in GC cells, and indicated a potential biomarker for prognostic prediction in GC.

Dataset Information

TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression

Publications

TUBA1C: a new potential target of LncRNA EGFR-AS1 promotes gastric cancer progression.

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