BACKGROUND: During the reproductive cycle of Scatophagus argus (S. argus), their gonads undergo degeneration and re-maturation including the degradation of proteins in the extracellular matrix (ECM). Matrix metalloproteinases (MMPs), a family of zinc proteases, play a crucial role in ECM degradation.
OBJECTIVE: Our aim was to identify the MMP gene family of S. argus and determine their gene expression levels across various stages of gonadal development.
METHODS: The MMP gene family of S. argus in the genome was identified by using basic Local Alignment Search Tool (BLAST) and HMMER. Phylogenetic tree and synteny analysis were performed to investigate the evolutionary past of the MMP gene family. The gonads of 18 S. argus (9 males and 9 females) were dissected and a quantitative reverse transcription polymerase chain reaction (RT-qPCR) was conducted to investigate the expression levels of MMP genes across different stages of gonadal development.
RESULTS: Twenty-three MMP family genes were identified in the genome of S. argus. We divided the MMP gene family into 4 categories and found that teleosts exhibit a higher MMP gene copy number relative to other vertebrates. By sampling S. argus at different stages of gonadal development, we observed an upregulation in relative expression levels of 11 MMP genes in the testis or ovary. Ten MMP genes (mmp2, 9, 14a, 15a, 15b, 16a, 17a, 23b and 24) showed higher mRNA expression in the testis compared to the ovary and mmp28 had higher expression during ovarian development. The tissue distribution results demonstrated that the gills exhibited the lowest relative expression level among all tissues examined. However, 6 genes (mmp2, 9, 14a, 15a, 15b, and 16a) had relatively high expression in all tissues.
CONCLUSIONS: The result suggested that teleost-special whole genome duplication was mainly responsible for the formation of the MMP gene family in teleosts. Expression patterns of MMP genes indicated that mmp2, 9, 14a, 15a, 15b, 16a, 17a, 23b and 24 played a vital role in testicular development while mmp28 was more important for ovarian development. Limitaion: Further studies are needed to determine their protein expressions in gonadal development and precise mechanism in gonadal differentiation. The study enhances our understanding of the MMP gene family in evolution of teleost and provides valuable insights for further research on MMPs in S. argus.

Kidney Renal Clear Cell Carcinoma (KIRC) is a malignant tumor that carries a substantial risk of morbidity and mortality. The MMP family assumes a crucial role in tumor invasion and metastasis. This study aimed to uncover the mechanistic relevance of the MMP gene family as a therapeutic target and diagnostic biomarker in Kidney Renal Clear Cell Carcinoma (KIRC) through a comprehensive approach encompassing both computational and molecular analyses. STRING, Cytoscape, UALCAN, GEPIA, OncoDB, HPA, cBioPortal, GSEA, TIMER, ENCORI, DrugBank, targeted bisulfite sequencing (bisulfite-seq), conventional PCR, Sanger sequencing, and RT-qPCR based analyses were used in the present study to analyze MMP gene family members to accurately determine a few hub genes that can be utilized as both therapeutic targets and diagnostic biomarkers for KIRC. By performing STRING and Cytohubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP12 (matrix metallopeptidase 12), and MMP16 (matrix metallopeptidase 16) genes were denoted as hub genes having highest degree scores. After analyzing MMP2, MMP9, MMP12, and MMP16 via various TCGA databases and RT-qPCR technique across clinical samples and KIRC cell lines, interestingly, all these hub genes were found significantly overexpressed at mRNA and protein levels in KIRC samples relative to controls. The notable effect of the up-regulated MMP2, MMP9, MMP12, and MMP16 was also documented on the overall survival (OS) of the KIRC patients. Moreover, targeted bisulfite-sequencing (bisulfite-seq) analysis revealed that promoter hypomethylation pattern was associated with up-regulation of hub genes (MMP2, MMP9, MMP12, and MMP16). In addition to this, hub genes were involved in various diverse oncogenic pathways. The MMP gene family members (MMP2, MMP9, MMP12, and MMP16) may serve as therapeutic targets and prognostic biomarkers in KIRC.

Renal cell carcinoma can arise from lesions in the renal epithelium. This particular type of cancer is prevalent in the realm of renal cancers and is associated with an unfavorable prognosis. Among these cases, over 70% are classified as kidney renal clear cell carcinoma (KIRC). Since the underlying causes of KIRC haven\'t been fully understood, there is an urgent need for deeper investigation into its pathogenesis. Various tools, software, and molecular analysis was used, including Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), Cytoscape, University of ALabama at Birmingham CANcer data analysis Portal (UALCAN), muTarget, Gene Expression Profiling Interactive Analysis (GEPIA), OncoDB, Human Protein Atlas (HPA), cBioPortal, Kaplan-Meier (KM) plotter, Gene Set Enrichment Analysis (GSEA), Tumor IMmune Estimation Resource (TIMER), Encyclopedia of RNA Interactomes (ENCORI), DrugBank, Encyclopedia of RNA Interactomes (RT-qPCR), targeted bisulfide sequencing (bisulfide-seq), and receiver operating curve (ROC) to matrix metallopeptidase (MMP) gene family constituents, with the precise objective of identifying a small set of hub genes. These hub genes hold the potential to be harnessed as molecular biomarkers for KIRC. By performing STRING and CytoHubba analyses of the 24 MMP gene family members, MMP2 (matrix metallopeptidase 2), MMP9 (matrix metallopeptidase 9), MMP14 (matrix metallopeptidase 14), and MMP16 (matrix metallopeptidase 16) were recognized as hub genes having highest degree scores. After conducting an in-depth expression analysis of MMP2, MMP9, MMP14, and MMP16 using various The Cancer Genome Atlas (TCGA) databases and RT-qPCR techniques, these displayed a significant increase in expression at both the mRNA and protein levels within KIRC samples when compared to control samples. The impact of the over expression of MMP2, MMP9, MMP14, and MMP16 also left a distinct mark on the worst overall survival (OS) rates of KIRC patients. Furthermore, a targeted bisulfide-seq investigation unveiled a correlation between promoter hypomethylation patterns and the up-regulation of these key genes in KIRC patients. Additionally, hub genes were involved in various diverse oncogenic pathways. In conclusion, four MMP gene family members, including MMP2, MMP9, MMP14, and MMP16 may serve as therapeutic target and molecular biomarker in KIRC.

The Matrix metalloproteinase (MMP) gene family is responsible for regulating the degradation of Extra Cellular Matrix (ECM) proteins, which are important for physiological processes such as wound healing, tissue remodeling, and stress response. Although MMPs have been studied in many species, their role in immune response in Japanese flounder (Paralichthys olivaceus) is still not fully understood. This study conducted a comprehensive analysis of MMPs in flounder, including gene structures, evolutionary relationships, conserved domains, molecular evolution, and expression patterns. Analysis revealed that MMP genes could be grouped into 17 subfamilies and were evolutionarily conserved and functionally-constrained. Meanwhile, MMP genes were found to express in different embryonic and larval stages and might play the role of sentinel in healthy tissues. Furthermore, expression profiling showed that MMPs had diverse functions in environmental stress, with 60% (9/15) and 73% (11/15) of MMPs showing differential expression patterns under temperature stress and Edwardsiella tarda (E. tarda) infection, respectively. These findings provide a useful resource for understanding the immune functions of MMP genes in Japanese flounder.