Bioinformatics analysis and validation of HAUS6 as a key prognostic gene in squamous cell carcinoma of the tongue.

OBJECTIVE: To explore the expression of HAUS6 in squamous cell carcinoma of the tongue (TSCC) and its relationship with the clinicopathological features of patients, and to further provide new ideas and therapeutic targets for curing TSCC. DESIGN: The Cancer Genome Atlas (TCGA) database was used to screen for differentially expressed genes (DEGs) between TSCC and normal tissues and survival analysis. DEGs of HAUS6 were screened and analyzed for GO, KEGG and GSEA enrichment. Exploring the correlation of HAUS6 with immune cell infiltration and immune checkpoint-related genes. The expression of HAUS6 in tumor and paraneoplastic tissues was confirmed by immunohistochemistry and Western Blot. RESULTS: Analysis of the TCGA database results showed that expression of HAUS6 mRNA was significantly enhanced and correlated with overall survival (OS, p < 0.05) in TSCC. HAUS6 expression correlated with the level of immune cell infiltration and immune checkpoint-related genes. Immunohistochemistry and Western Blot confirmed that the expression level of HAUS6 protein was significantly higher in tumor tissues than in paraneoplastic tissues, and that tumor size and hypo-differentiation were higher in the HAUS6 high expression group than in the low expression group in TSCC (p < 0.05). CONCLUSIONS: In conclusion, these analyses suggest that HAUS6 can act as an independent predictor of prognosis (p < 0.05) and high HAUS6 expression is strongly associated with poor prognosis.

Phenotype-genotype mapping reveals the betaine-triggered L-arginine overproduction mechanism in Escherichia coli.

The production phenotype improvement of industrial microbes is extremely needed and challenging. Environmental factors optimization provides insightful ideas to trigger the superior production phenotype by activating potential genetic determiners. Here, phenotype-genotype mapping was used to dissect the betaine-triggered L-arginine overproduction mechanism and mine beneficial genes for further improving production phenotype. The comparative transcriptomic analysis revealed a novel role for betaine in modulating global gene transcription. Guided by this finding, 4 novel genes (cynX, cynT, pyrB, and rhaB) for L-arginine biosynthesis were identified via reverse engineering. Moreover, the rhaB deletion was demonstrated as a common metabolic engineering strategy to improve ATP pool in E. coli. By combinatorial genes manipulation, the L-arginine titer and yield increased by 17.9% and 28.9% in a 5-L bioreactor without betaine addition. This study revealed the molecular mechanism of gene transcription regulation by betaine and developed a superior L-arginine overproducer that does not require betaine.