Yadav Monika, Pradhan Dibyabhaba, Singh Rana P
Cancer Biology Laboratory, School of Life Sciences, Jawaharlal Nehru University, New Delhi, 110067 India.
ICMR-AIIMS Computational Genomics Centre, New Delhi, India.
3 Biotech. 2021 May;11(5):215. doi: 10.1007/s13205-021-02737-4. Epub 2021 Apr 14.
Oral squamous cell carcinoma (OSCC) is one of the leading cancers with poor disease survival rate. Herein, we explored molecular basis, in silico identification and in vitro verification of genes associated with OSCC. Five gene expression series including, GSE30784, GSE13601, GSE9844, GSE23558 and GSE37991 were screened for differentially expressed genes (DEGs). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched by cluster Profiler. Further, protein-protein interaction network was analysed and hub genes were verified. A total of 6476 (up-regulated: 2848; down-regulated: 3628) DEGs were identified among OSCC patients and healthy controls. Gene Ontology analysis indicated DEGs enrichment in cellular motility, invasion and adhesion processes. KEGG analysis revealed enrichment of PI3K-Akt signalling, focal adhesion and regulation of actin cytoskeleton pathways. Subsequently, nine DEGs including were correlated with TCGA expression data along with significant association towards patient's survival, recognized as hub genes. This dysregulated mRNA signature of genes was validated in two OSCC cell lines with an anti-cancer agent, fisetin. Fisetin inhibited the expression of and upregulated the expression of gene which were associated with growth inhibition of both the OSCC cell lines. The regulatory effect of fisetin supported crucial role of nine hub genes identified in OSCC. This study signified that hub genes and pathways might influence the aggressiveness of OSCC. Thus, the proposed hub genes could be potential diagnostic biomarker and drug targets for OSCC.
The online version contains supplementary material available at 10.1007/s13205-021-02737-4.
口腔鳞状细胞癌（OSCC）是疾病生存率较低的主要癌症之一。在此，我们探讨了与OSCC相关基因的分子基础、计算机识别和体外验证。筛选了包括GSE30784、GSE13601、GSE9844、GSE23558和GSE37991在内的五个基因表达系列，以寻找差异表达基因（DEG）。通过cluster Profiler对基因本体论和京都基因与基因组百科全书（KEGG）通路进行了富集分析。此外，分析了蛋白质-蛋白质相互作用网络并验证了枢纽基因。在OSCC患者和健康对照中总共鉴定出6476个DEG（上调：2848个；下调：3628个）。基因本体论分析表明DEG在细胞运动、侵袭和黏附过程中富集。KEGG分析揭示了PI3K-Akt信号通路、粘着斑和肌动蛋白细胞骨架调节通路的富集。随后，包括 在内的9个DEG与TCGA表达数据相关，并且与患者生存率有显著关联，被识别为枢纽基因。用抗癌剂非瑟酮在两种OSCC细胞系中验证了这种基因失调的mRNA特征。非瑟酮抑制了 的表达并上调了 基因的表达，这与两种OSCC细胞系的生长抑制相关。非瑟酮的调节作用支持了在OSCC中鉴定出的9个枢纽基因的关键作用。这项研究表明枢纽基因和通路可能影响OSCC的侵袭性。因此，所提出的枢纽基因可能是OSCC潜在的诊断生物标志物和药物靶点。
在线版本包含可在10.1007/s13205-021-02737-4获取的补充材料。
