The Expression of the Immunoproteasome Subunit PSMB9 Is Related to Distinct Molecular Subtypes of Uterine Leiomyosarcoma

Falcão, Raul Maia; Kokaraki, Georgia; Wispelaere, Wout De; Amant, Frédéric; Souza, Gustavo; Souza, Jorge Estefano Santana de; Carlson, Joseph W.; Petta, Tirzah Braz

doi:10.3390/cancers14205007

Cited by 7 publications

(3 citation statements)

References 28 publications

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“…Proteasomes play a key role in the stress response because they degrade damaged proteins 90 . PSMB9 is also a potential diagnostic biomarker and tumor suppressor for human uterine leiomyosarcoma 91 . ANXA8L2 Protein 2, ANXA8 protein (annexin A8), and ANXA8L1 protein 1 are members of the annexin family of evolutionarily conserved Ca 2 + and phospholipid-binding proteins; their overexpression has been associated with acute myelocytic leukemia 32 .…”

Section: Resultsmentioning

confidence: 99%

Identification of modules and key genes associated with breast cancer subtypes through network analysis

Mares-Quiñones,

Galán-Vásquez,

Pérez-Rueda

et al. 2024

Sci Rep

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Breast cancer is the most common malignancy in women around the world. Intratumor and intertumoral heterogeneity persist in mammary tumors. Therefore, the identification of biomarkers is essential for the treatment of this malignancy. This study analyzed 28,143 genes expressed in 49 breast cancer cell lines using a Weighted Gene Co-expression Network Analysis to determine specific target proteins for Basal A, Basal B, Luminal A, Luminal B, and HER2 ampl breast cancer subtypes. Sixty-five modules were identified, of which five were characterized as having a high correlation with breast cancer subtypes. Genes overexpressed in the tumor were found to participate in the following mechanisms: regulation of the apoptotic process, transcriptional regulation, angiogenesis, signaling, and cellular survival. In particular, we identified the following genes, considered as hubs: IFIT3, an inhibitor of viral and cellular processes; ETS1, a transcription factor involved in cell death and tumorigenesis; ENSG00000259723 lncRNA, expressed in cancers; AL033519.3, a hypothetical gene; and TMEM86A, important for regulating keratinocyte membrane properties, considered as a key in Basal A, Basal B, Luminal A, Luminal B, and HER2 ampl breast cancer subtypes, respectively. The modules and genes identified in this work can be used to identify possible biomarkers or therapeutic targets in different breast cancer subtypes.

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Section: Resultsmentioning

confidence: 99%

Identification of modules and key genes associated with breast cancer subtypes through network analysis

Mares-Quiñones,

Galán-Vásquez,

Pérez-Rueda

et al. 2024

Sci Rep

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“…Bioinformatic analysis was conducted as previously described [ 26 ]. Specifically, preprocessing, mapping and counting RNA‐Seq reads: each fastq file was assessed using fastqc (v0.11.9) followed by adapter removing and trimming bad quality base calling with trim‐galore (v0.6.6) when it was detected in the quality report.…”

Section: Methodsmentioning

confidence: 99%

MMP14 expression and collagen remodelling support uterine leiomyosarcoma aggressiveness

et al. 2023

Self Cite

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Fibrillar collagen deposition, stiffness and downstream signalling support the development of leiomyomas (LMs), common benign mesenchymal tumours of the uterus, and are associated with aggressiveness in multiple carcinomas. Compared with epithelial carcinomas, however, the impact of fibrillar collagens on malignant mesenchymal tumours, including uterine leiomyosarcoma (uLMS), remains elusive. In this study, we analyse the network morphology and density of fibrillar collagens combined with the gene expression within uLMS, LM and normal myometrium (MM). We find that, in contrast to LM, uLMS tumours present low collagen density and increased expression of collagen‐remodelling genes, features associated with tumour aggressiveness. Using collagen‐based 3D matrices, we show that matrix metalloproteinase‐14 (MMP14), a central protein with collagen‐remodelling functions that is particularly overexpressed in uLMS, supports uLMS cell proliferation. In addition, we find that, unlike MM and LM cells, uLMS proliferation and migration are less sensitive to changes in collagen substrate stiffness. We demonstrate that uLMS cell growth in low‐stiffness substrates is sustained by an enhanced basal yes‐associated protein 1 (YAP) activity. Altogether, our results indicate that uLMS cells acquire increased collagen remodelling capabilities and are adapted to grow and migrate in low collagen and soft microenvironments. These results further suggest that matrix remodelling and YAP are potential therapeutic targets for this deadly disease.

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“…Despite being essential in cellular and immunological functions, the role of PSMB8 and PSMB9 has not been determined in all types of cancers, as highlighted in at least 78 publications [16], including 19 meta-analyses [17]. Few molecular genetics studies have focused on relationships between these i-proteasome genes and bladder cancer [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma

Elhawary¹,

Ekram²,

Abumansour³

et al. 2023

Cureus

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Background: The PSMB8 and PSMB9 immunoproteasome genes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) in PSMB9 and PSMB8. We determined any associations between these SNPs and susceptibility to UBC in the Saudi community.Methods: Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for the PSMB9 rs17587 G>A and PSMB8 rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model.Results: The PSMB9 rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21, P < 0.0001). In contrast, the PSMB8 rs2071543 SNP showed no association with UBC risk (OR = 1.13, P = 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1; P = 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4; P = 0.0026) models. Genotypic distribution of the PSMB8 rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models (P > 0.05).Conclusion: These results suggest a potential role for PSMB9 as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk.

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The Expression of the Immunoproteasome Subunit PSMB9 Is Related to Distinct Molecular Subtypes of Uterine Leiomyosarcoma

Cited by 7 publications

References 28 publications

Identification of modules and key genes associated with breast cancer subtypes through network analysis

Identification of modules and key genes associated with breast cancer subtypes through network analysis

MMP14 expression and collagen remodelling support uterine leiomyosarcoma aggressiveness

Sequence Variants in PSMB8/PSMB9 Immunoproteasome Genes and Risk of Urothelial Bladder Carcinoma

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