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MAPKAPK2-centric transcriptome profiling reveals its major role in governing molecular crosstalk of IGFBP2, MUC4, and

Sourabh Soni1,2, Prince Anand1,2, Mohit Kumar Swarnkar3

  • 1Pharmacology and Toxicology Laboratory, CSIR-Institute of Himalayan Bioresource Technology (CSIR-IHBT), Palampur 176061, India.

Computational and Structural Biotechnology Journal
|February 23, 2023
PubMed

Insights

This study reveals key genes regulated by MAPKAPK2 (MK2) in head and neck squamous cell carcinoma (HNSCC). These MK2-controlled genes offer potential new targets for HNSCC diagnosis and treatment.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genomics

Background:

  • Head and neck squamous cell carcinoma (HNSCC) biology is complex.
  • MAPKAPK2 (MK2) influences mRNA turnover in HNSCC progression.
  • MK2's specific role in HNSCC tumor transcriptomes is not fully understood.

Purpose of the Study:

  • To investigate the biological relevance and molecular interactions of MK2 in HNSCC.
  • To identify MK2-regulated genes and their role in HNSCC pathogenesis.
  • To explore MK2's function in regulating mRNA turnover within the tumor microenvironment.

Main Methods:

  • Next-generation sequencing for transcriptome profiling of HNSCC cells and xenografts.
  • Differential gene expression analysis and regulatory network construction.
  • Validation using gene expression assays, immunohistochemistry, and transcript stability studies.

Main Results:

  • A set of crucial MK2-regulated candidate genes involved in HNSCC pathogenesis were identified.
  • 3'-UTR analysis pinpointed downstream MK2 target genes, including IGFBP2, MUC4, and PRKAR2B.
  • MK2 was shown to potentially regulate the transcript turnover of specific genes in HNSCC.

Conclusions:

  • This study identified novel MK2-regulated genes in HNSCC.
  • The findings elucidate the plausible involvement of these genes in HNSCC development.
  • These identified genes represent potential targets for HNSCC diagnostics and therapeutics.
Keywords:
3'-UTR3′-UTR, 3′-untranslated regionAREs, Adenylate-uridylate-rich element(s)ATCC, American Type Culture CollectionActD, Actinomycin DCISBP, Catalog of Inferred Sequence Binding PreferencesCt, Cycle ThresholdDAP3, Death associated protein 3DEGs, Differentially expressed gene(s)Differentially expressed genesEHBP1, EH domain binding protein 1FC, Fold changeFDR, False discovery rateFPKM, Fragments per kilobase of transcript per million mappedGFP, Green fluorescent proteinGO, Gene OntologyHKG, House-keeping genesHNSCCHNSCCs, Head and neck squamous cell carcinoma(s)HQ, High qualityIAEC, Institutional animal ethics committeeIFN, InterferonIGFBP2, Insulin-like growth factor-binding protein 2IHC, ImmunohistochemistryIP6K2, Inositol hexakisphosphate kinase 2KD, KnockdownKEGG, Kyoto encyclopedia of genes and genomicsMAPK, Mitogen-Activated Protein KinaseMAPKAPK2MAPKAPK2 or MK2, Mitogen-activated protein kinase-activated protein kinase 2MELK, Maternal embryonic leucine zipper kinaseMK2KD, MK2-knockdownMK2WT, MK2 wild-typeMKP-1, Mitogen-activated protein kinase phosphatase-1MUC4, Mucin 4NGS, Next generation sequencingNOD/SCID, Non-obese diabetic/severe combined immunodeficientPRKAR2B, Protein kinase CAMP-dependent type II regulatory subunit betaQC, Quality controlRBPs, RNA-binding protein(s)RIN, RNA integrity numberRNA-seq, Ribose Nucleic Acid -sequencingRNA-sequencingRT-qPCR, Real-time quantitative polymerase chain reactionRUNX1, Runt-related transcription factor 1SLF2, SMC5-SMC6 complex localization factor 2TCGA, The cancer genome atlasTNF-α, Tumor necrosis factor-alphaTTP, TristetraprolinTranscriptomeVEGF, Vascular endothelial growth factorWB, Western blottingWT, Wild typeZNF662, Zinc finger protein 662p27, Cyclin-dependent kinase inhibitor 1BshRNA, Short hairpin RNA

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