MAPKAPK2-centric transcriptome profiling reveals its major role in governing molecular crosstalk of IGFBP2, MUC4, and PRKAR2B during HNSCC pathogenesis.
Computational and structural biotechnology journal（2023）
摘要
Transcriptome analysis of head and neck squamous cell carcinoma (HNSCC) has been pivotal to comprehending the convoluted biology of HNSCC tumors. MAPKAPK2 or MK2 is a critical modulator of the mRNA turnover of crucial genes involved in HNSCC progression. However, MK2-centric transcriptome profiles of tumors are not well known. This study delves into HNSCC progression with MK2 at the nexus to delineate the biological relevance and intricate crosstalk of MK2 in the tumor milieu. We performed next-generation sequencing-based transcriptome profiling of HNSCC cells and xenograft tumors to ascertain mRNA expression profiles in MK2-wild type and MK2-knockdown conditions. The findings were validated using gene expression assays, immunohistochemistry, and transcript turnover studies. Here, we identified a pool of crucial MK2-regulated candidate genes by annotation and differential gene expression analyses. Regulatory network and pathway enrichment revealed their significance and involvement in the HNSCC pathogenesis. Additionally, 3'-UTR-based filtering recognized important MK2-regulated downstream target genes and validated them by nCounter gene expression assays. Finally, immunohistochemistry and transcript stability studies revealed the putative role of MK2 in regulating the transcript turnover of IGFBP2, MUC4, and PRKAR2B in HNSCC. Conclusively, MK2-regulated candidate genes were identified in this study, and their plausible involvement in HNSCC pathogenesis was elucidated. These genes possess investigative values as targets for diagnosis and therapeutic interventions for HNSCC.
更多查看译文
关键词
3'-UTR,3′-UTR, 3′-untranslated region,AREs, Adenylate-uridylate-rich element(s),ATCC, American Type Culture Collection,ActD, Actinomycin D,CISBP, Catalog of Inferred Sequence Binding Preferences,Ct, Cycle Threshold,DAP3, Death associated protein 3,DEGs, Differentially expressed gene(s),Differentially expressed genes,EHBP1, EH domain binding protein 1,FC, Fold change,FDR, False discovery rate,FPKM, Fragments per kilobase of transcript per million mapped,GFP, Green fluorescent protein,GO, Gene Ontology,HKG, House-keeping genes,HNSCC,HNSCCs, Head and neck squamous cell carcinoma(s),HQ, High quality,IAEC, Institutional animal ethics committee,IFN, Interferon,IGFBP2, Insulin-like growth factor-binding protein 2,IHC, Immunohistochemistry,IP6K2, Inositol hexakisphosphate kinase 2,KD, Knockdown,KEGG, Kyoto encyclopedia of genes and genomics,MAPK, Mitogen-Activated Protein Kinase,MAPKAPK2,MAPKAPK2 or MK2, Mitogen-activated protein kinase-activated protein kinase 2,MELK, Maternal embryonic leucine zipper kinase,MK2KD, MK2-knockdown,MK2WT, MK2 wild-type,MKP-1, Mitogen-activated protein kinase phosphatase-1,MUC4, Mucin 4,NGS, Next generation sequencing,NOD/SCID, Non-obese diabetic/severe combined immunodeficient,PRKAR2B, Protein kinase CAMP-dependent type II regulatory subunit beta,QC, Quality control,RBPs, RNA-binding protein(s),RIN, RNA integrity number,RNA-seq, Ribose Nucleic Acid -sequencing,RNA-sequencing,RT-qPCR, Real-time quantitative polymerase chain reaction,RUNX1, Runt-related transcription factor 1,SLF2, SMC5-SMC6 complex localization factor 2,TCGA, The cancer genome atlas,TNF-α, Tumor necrosis factor-alpha,TTP, Tristetraprolin,Transcriptome,VEGF, Vascular endothelial growth factor,WB, Western blotting,WT, Wild type,ZNF662, Zinc finger protein 662,p27, Cyclin-dependent kinase inhibitor 1B,shRNA, Short hairpin RNA
AI 理解论文
溯源树
样例
生成溯源树，研究论文发展脉络
Chat Paper
正在生成论文摘要