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

来  源：   DOI：10.1016/j.csbj.2023.01.039   PDF(Pubmed)

Abstract：
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.
摘要：
头颈部鳞状细胞癌（HNSCC）的转录组分析对于理解HNSCC肿瘤的复杂生物学至关重要。MAPKAPK2或MK2是参与HNSCC进展的关键基因的mRNA转换的关键调节剂。然而,肿瘤的以MK2为中心的转录组概况尚不清楚。这项研究探讨了HNSCC与MK2在连接处的进展，以描绘肿瘤环境中MK2的生物学相关性和复杂的串扰。我们对HNSCC细胞和异种移植肿瘤进行了基于下一代测序的转录组分析，以确定MK2野生型和MK2敲低条件下的mRNA表达谱。使用基因表达测定验证了这些发现，免疫组织化学，和成绩单营业额研究。这里,我们通过注释和差异基因表达分析鉴定了一组关键的MK2调控候选基因.调节网络和途径富集揭示了它们在HNSCC发病机理中的重要性和参与。此外,基于3'-UTR的过滤识别了重要的MK2调节的下游靶基因，并通过nCounter基因表达测定对其进行了验证。最后,免疫组织化学和转录稳定性研究揭示了MK2在调节HNSCC中IGFBP2，MUC4和PRKAR2B的转录转换中的推定作用。最后，在这项研究中鉴定了MK2调节的候选基因，阐明了它们在HNSCC发病机制中的可能参与。这些基因具有作为HNSCC的诊断和治疗干预的目标的研究价值。
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