Bioinformatics based exploration of hsa-miR-194-5p regulation of CHD4 through PI3K/AKT signal pathway to enhance tumor resistance to apoptosis due to loss of nests and participate in poor prognosis of oral squamous cell carcinoma

Abstract

Background Recent evidence shows that CHD4 is involved in a variety of biological events of tumors. Our aim was to investigate the correlation between CHD4 and oral squamous cell carcinoma (OSCC). Methods After CHD4 was screened as a differentially expressed gene in The Cancer Genome Atlas (TGCA) database, the correlations of its expression level with the clinical parameters and prognosis of patients with OSCC were analyzed. The outcomes of the multivariate analysis were used to construct a nomogram, and the accuracy of the model was evaluated with the calibration curve. The GeneMANIA and STRING databases were used to generate network diagrams depicting interactions of genes with CHD4, and heat maps of genes co-expressed with CHD4 were generated using the TCGA database. TargetScan was then used to look into the miRNAs that interact with the 3' untranslated region of CHD4 mRNA. Finally, GSEA enrichment analysis was used to explore the possible mechanism. Results The differentially expressed molecule CHD4 was screened by TCGA database for OSCC. CHD4 was overexpressed in OSCC tumor tissues, and OSCC patients with low expression of CHD4 have better OS and DSS. The nomogram had a C-index of 0.575 (0.548–0.602), which indicated some degree of predictive reliability. CHD4 has certain correlation with exons of OSCC related genes, including TP53 , NOTCH1 , CASP8 , PTEN , TP63 , ANXA1 , CDH1 , CTNNB1 , GDF15 and EGFR . According to the TargetScan database, hsa-miR-194-5p is the miRNA that regulates CHD4 upstream the most. GSEA analysis showed that CHD4 may participate in the poor prognosis of OSCC by participating in PI3K/AKT pathway, protein adhesion regulation, MAPK pathway, cytokine and inflammatory response regulation, angiogenesis and platelet regulation. Conclusions The decreased expression of CHD4 may indicate a better prognosis in OSCC patients and could serve as a novel predictive biomarker for OSCC. Also, hsa-miR-194-5p was found to contribute to the poor prognosis of OSCC by regulating CHD4 and enhancing tumor anoikis resistance via the PI3K/AKT signaling pathway. These findings suggest that CHD4 might be a therapeutic target for the effective treatment of OSCC.

Identification and validation of a prognostic anoikis-related gene signature in papillary thyroid carcinoma by integrated analysis of single-cell and bulk RNA-sequencing

“…[ 19 ] Anoikis is a physiologically programmed apoptosis, which could maintain tissue homeostasis through eliminating detached cells. [ 20 ] Moreover, anoikis has been considered as an essential factor in promoting tumor metastasis. [ 21 ] Thus, anoikis may be involved in the development of PTC.…”