Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas
Abstract
:1. Introduction
2. Results
2.1. High-Throughput Sequencing of Coding RNA Transcripts in Leiomyoma and Matched Myometrium
2.2. Differential Expression of MED12-Associated Coding RNA Transcripts in Leiomyoma and Matched Myometrium
2.3. Differential Expression of MED12-Associated Coding RNA Transcripts in Myometrium
2.4. Validation of MED12-Associated Coding RNA Transcripts in Leiomyoma and Matched Myometrium
3. Discussion
4. Materials and Methods
4.1. Myometrium and Leiomyoma Tissue Collection
4.2. MED12-Mutation Analysis
4.3. RNA Sequencing and Bioinformatic Analysis
4.4. Quantitative RT-PCR
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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GO/KEGG Pathway Enrichment | Symbol | Lyo vs Myo | Lyo/Myo(+) vs Lyo/Myo(−) | Lyo(+) vs Lyo(−) | Myo(+) vs Myo(−) | Function |
---|---|---|---|---|---|---|
ECM-receptor interaction | COL11A1 | Up (p < 0.001) | Up (p < 0.001) | Up (p < 0.001) | No Significance | Minor fibrillar collagen; expression has been associated with advanced tumorigenic disease and epithelial-mesenchymal transition (EMT) [37]. |
ECM-receptor interaction | MUC12 | Up (p < 0.05) | Up (p < 0.05) | Up (p < 0.05) | No Significance | An O-glycosylated protein of the mucin family; mucous barrier on epithelial surfaces; involves in adhesion modulation, epithelial renewal, differentiation and intracellular signaling via EGF-like domains in its extracellular region [38]. |
ECM-receptor interaction | FRMD5 | Up (p < 0.001) | Up (p < 0.001) | Up (p < 0.001) | No Significance | Part of adherens junction and involved in regulation of cell migration, cellular metabolism, and signal transduction [39,40]. |
ECM-receptor interaction | FCGBP | Up (p < 0.001) | Up (p < 0.001) | Up (p < 0.001) | No Significance | Contains multiple von Willebrand D (VWD) domains that form complexes through disulfide-linked heterodimers with members of the mucin and trefoil factor family, which affect the attachment and motility of pathogens on mucosal surfaces [41,42]. |
ECM-receptor interaction | EGFL6 | Up (p < 0.001) | Up (p < 0.001) | Up (p < 0.001) | No Significance | Member of EGF superfamily, is expressed at significant levels during developmental processes and various malignant cancers; involved in the regulation of cell cycle, tumor proliferation, invasion, and metastasis through activation of multiple signaling pathways including PI3K/AKT, ERK/MAPK, Wnt/β-catenin and integrin-mediated signaling pathway [43]. |
ECM-receptor interaction | FN1 | Up (p < 0.001) | Up (p < 0.01) | Up (p < 0.01) | No Significance | A major component of the extracellular matrix, exists as a dimeric or multimeric form with other extracellular matrix proteins such as integrins, collagen, fibrin, and heparan sulfate proteoglycans linked by disulfide bonds [44,45]. |
ECM-receptor interaction | KLK5 | Up (p < 0.01) | Up (p < 0.01) | Up (p < 0.001) | No Significance | KLK5, a member of the kallikrein subfamily, is involved in collagen formation and MSP-RON signaling [46,47]. |
ECM-receptor interaction | ITGA9 | Up (p < 0.001) | Up (p < 0.01) | Up (p < 0.01) | No Significance | An integrin subunit that mediates cell-cell and cell-matrix adhesion and accelerates cell migration and regulates various biological functions including cancer cell proliferation, angiogenesis, adhesion and invasion [48]. |
ECM-receptor interaction | DCX | Up (p < 0.001) | No Significance | Up (p < 0.001) | Up (p < 0.01) | A microtubule-associated protein, contains two internal tandem repeats and stabilizes microtubules through bundling to the microtubule cytoskeleton [49]. |
Cell signaling pathway | WNT4 | Up (p < 0.01) | Up (p < 0.01) | Up (p < 0.001) | No Significance | Ligand for members of the frizzled family of seven transmembrane receptors; works as a biphasic initiator for activating the canonical and non-canonical Wnt signaling [50]. |
Cell signaling pathway | WNT2 | Up (p < 0.01) | Up (p < 0.05) | Up (p < 0.01) | No Significance | Enriched in cancer-associated fibroblasts; has the potential to enhance the growth and invasion of colorectal cancer [50]. |
Cell signaling pathway | WNT16 | Up (p < 0.001) | Up (p < 0.01) | Up (p < 0.001) | Up (p < 0.01) | Has no homology to any other Wnts signaling molecule; implicated in tumorigenesis and in skeletal development and postnatal bone homeostasis [50]. |
Cell signaling pathway | CXCL13 | Up (p < 0.001) | Up (p < 0.01) | Up (p < 0.01) | No Significance | Potent B lymphocyte chemoattractant, which promotes the migration of B lymphocytes, and is one of the most abundant chemokines in endometrial epithelial cells [51]. |
Cell signaling pathway | CBX8 | Up (p < 0.001) | Up (p < 0.001) | Up (p < 0.001) | No Significance | Component of a PcG PRC1-like complex, is involved in the RNA polymerase II-mediated transcription repression of genes [52]. |
Cell signaling pathway | S100A1 | Down (p < 0.001) | Down (p < 0.05) | No Significance | No Significance | Member of the S100 family of calcium-binding proteins; interacts with specific target proteins, resulting in the modulation of their activity [53,54]. |
Cell signaling pathway | NDC80 | Up (p < 0.001) | Up (p < 0.05) | Up (p < 0.05) | No Significance | Component of the essential kinetochore-related NDC80 complex, which is involved in the organization and stabilization of microtubule-kinetochore interactions, spindle checkpoint signaling and chromosome segregation [55]. |
Cell signaling pathway | NTM | Up (p < 0.001) | Up (p < 0.001) | Up (p < 0.001) | No Significance | Neural cell adhesion molecule, promotes adhesion and neurite outgrowth via a homophilic mechanism [56]. |
Cell signaling pathway | RAB37 | Down (p < 0.001) | Down (p < 0.001) | Down (p < 0.001) | No Significance | Rab small GTPase protein, through switching its guanine nucleotide binding status between GDP-bound (inactive) and GTP-bound (active) functions as a critical regulator in exocytotic pathway [57]. |
Cell signaling pathway | PPP1R14C | Up (p < 0.001) | Up (p < 0.05) | Up (p < 0.01) | No Significance | Inhibitor of the PP1 serine/threonine phosphatase, which regulates the activation of PTH(1–34)-induced catabolic response and the non-canonical PTH1R signaling pathway [58,59]. |
Cell signaling pathway | JAK3 | No Significance | Up (p < 0.01) | Up (p < 0.01) | No Significance | Member of the JAK family of non-receptor tyrosine kinases, plays a pivotal role in cytokine and growth factor-mediated intracellular signal transduction via the JAK/STAT pathway [60]. |
Cell signaling pathway | WIF1 | Up (p < 0.001) | No Significance | No Significance | Up (p < 0.01) | Secreted protein that binds and inhibits the activity of Wnt proteins.Downregulated in numerous cancers via epigenetic transcriptional silencing mechanism [61,62]. |
Cell signaling pathway | BMP7 | Up (p < 0.001) | No Significance | Up (p < 0.05) | No Significance | Secreted ligand of the TGF-β superfamily, activates TGF-β signaling via receptor-mediated activation of Smad transcription factors leading to target genes regulation [63]. |
Metabolic pathways | EZH2 | Up (p < 0.001) | Up (p < 0.01) | Up (p < 0.01) | No Significance | Catalytic core protein in PRC2 and facilitated PRC2-mediated H3K27me3 reaction. The dysregulation of EZH2 is acting as an important driver of tumorigenesis and progression [64]. |
Metabolic pathways | IGFBPL1 | Up (p < 0.05) | Up (p < 0.001) | Up (p < 0.01) | No Significance | Located in extracellular space, is an IGF-binding protein that could prolong the half-life of IGF proteins and either promotes or inhibits the effects of IGF proteins on cell growth [65]. |
Metabolic pathways | MTMR8 | Up (p < 0.001) | Up (p < 0.05) | No Significance | Down (p < 0.05) | Member of the myotubularin-related family; has phosphatase activity towards lipids containing phosphoinositol headgroup and acts on phosphatidylinositol 3-phosphate and phosphatidylinositol 3,5-bisphosphate; functions in membrane trafficking, cytoskeletal regulation, and receptor signaling [66]. |
Metabolic pathways | ATP5MC1P1 | Up (p < 0.001) | Up (p < 0.05) | Up (p < 0.01) | No Significance | Pseudogene of ATP5MC1, which is encoded by the mitochondrial DNA and is subunit c of mitochondrial ATP synthase (F1F0 ATP synthase or Complex V) [67]. |
Metabolic pathways | CYP19A1 | Up (p < 0.001) | No Significance | Up (p < 0.05) | No Significance | Member of the cytochrome P450 superfamily, is a monooxygenase involved in many reactions such as synthesis of steroids, lipids, cholesterol, and drug metabolism [68]. |
Transcription regulation | S100A4 | Down (p < 0.001) | Down (p < 0.01) | Down (p < 0.01) | No Significance | Member of the S100 calcium-binding protein family, through its interaction with other proteins plays essential roles in many cellular processes and the development of cancers including metastasis, differentiation, inflammation, metastasis, and cell cycle progression [69]. |
Transcription regulation | HMX1 | Up (p < 0.001) | Up (p < 0.01) | Up (p < 0.01) | No Significance | Transcription factor that belongs to the homeobox proteins (H6 family), and it recognizes and binds to the 5′-CAAG-3′ core DNA sequence. HMX1 may act as a transcriptional repressor and involved in the development of craniofacial structures [70]. |
Ion homeostasis | CACNA1D | Up (p < 0.001) | No Significance | Up (p < 0.05) | Up (p < 0.01) | Member of the high-voltage-activated Ca2+ channels (HVA), is expressed in uterus and involved in a variety of calcium signaling related processes [71]. |
Ion homeostasis | RGS4 | Up (p < 0.001) | No Significance | Up (p < 0.01) | No Significance | Regulates numerous G protein-coupled receptors (GPCRs) associated post-receptor signaling cascades [72]. |
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Chuang, T.-D.; Gao, J.; Quintanilla, D.; McSwiggin, H.; Boos, D.; Yan, W.; Khorram, O. Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas. Int. J. Mol. Sci. 2023, 24, 3742. https://doi.org/10.3390/ijms24043742
Chuang T-D, Gao J, Quintanilla D, McSwiggin H, Boos D, Yan W, Khorram O. Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas. International Journal of Molecular Sciences. 2023; 24(4):3742. https://doi.org/10.3390/ijms24043742
Chicago/Turabian StyleChuang, Tsai-Der, Jianjun Gao, Derek Quintanilla, Hayden McSwiggin, Drake Boos, Wei Yan, and Omid Khorram. 2023. "Differential Expression of MED12-Associated Coding RNA Transcripts in Uterine Leiomyomas" International Journal of Molecular Sciences 24, no. 4: 3742. https://doi.org/10.3390/ijms24043742