Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2

Pereira, Márcia S.; Celeiro, Sónia Pires; Costa, Ângela M.; Pinto, Filipe; Popov, Sergey; Almeida, Gisele Caravina de; Amorim, Júlia; Pires, Manuel Melo; Pinheiro, Célia; Lopes, José Manuel; Honavar, Mrinalini; Costa, Paulo; Pimentel, José; Jones, Chris; Reis, Rui Manuel; Viana-Pereira, Marta

doi:10.1007/s13402-019-00475-7

Cited by 8 publications

(9 citation statements)

References 54 publications

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“…SPINT2, the identified GMR of the profiled PTC ( Figure 6), was previously reported by several groups to be involved in the development and progression of a wide diversity of forms of cancer [53]. Among others, SPINT2 was associated with metastatic osteosarcoma [54], ovarian cancer [55], glioma/glioblastoma [56,57], prostate cancer [58] and non-small lung cancer [59], leukemia [60] and cervical carcinoma [61]. RPAP3, essential for assembling chaperone complexes [62], was linked to hypoxia-adapted cancer cells [63] and BZW,1 was associated with ovarian [64], lung [65] and salivary gland [66] cancers.…”

mentioning

confidence: 69%

Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

Iacobaş

2020

Genes

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Publicly available (own) transcriptomic data have been analyzed to quantify the alteration in functional pathways in thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data have been generated by profiling one case of papillary thyroid carcinoma (PTC) and genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric paradigm that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase in the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that SPINT2 experimental overexpression may force the PTC cells into apoptosis with a negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cell lines before and after lentiviral transfection with DDX19B.

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confidence: 69%

Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

Iacobaş

2020

Genes

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“…6), was previously reported by several groups as involved in the development and progression of wide diversity forms of cancer [45]. Among others, SPINT2 was associated with metastatic osteosarcoma [46], ovarian cancer [47], glioma/glioblastoma [48,49], prostate [50] and non-small lung [51] cancers, leukemia [52] and cervical carcinoma [53]. RPAP3, essential for assembling chaperone complexes [54], was linked to hypoxia adapted cancer cells [55] and BZW,1 was associated with ovarian [56], lung [57] and salivary gland [58] cancers.…”

Section: Discussionmentioning

confidence: 87%

Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

Iacobaş

2020

Preprint

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Publically available (own) transcriptomic data were re-analyzed to quantify the alteration of functional pathways in the thyroid cancer, establish the gene hierarchy, identify potential gene targets and predict the effects of their manipulation. The expression data were generated from one case of papillary thyroid carcinoma (PTC) and from genetically manipulated BCPAP (papillary) and 8505C (anaplastic) human thyroid cancer cell lines. The study used the genomic fabric perspective that considers the transcriptome as a multi-dimensional mathematical object based on the three independent characteristics that can be derived for each gene from the expression data. We found remarkable remodeling of the thyroid hormone synthesis, cell cycle, oxidative phosphorylation and apoptosis pathways. Serine peptidase inhibitor, Kunitz type, 2 (SPINT2) was identified as the Gene Master Regulator of the investigated PTC. The substantial increase of the expression synergism of SPINT2 with apoptosis genes in the cancer nodule with respect to the surrounding normal tissue (NOR) suggests that its experimental overexpression may force the PTC cells into apoptosis with negligible effect on the NOR cells. The predictive value of the expression coordination for the expression regulation was validated with data from 8505C and BCPAP cells before and after lentiviral transfection with DDX19B.

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“…MMP2 is one of the most important proteases that mediate fibrillar collagen degradation. Several studies have indicated that MMP2 promotes the migration and invasion of glioma cells ( 28 ), lung cancer cells ( 29 ), and RA-FLSs ( 30 , 31 ). Thus, we sought to determine whether Circ_0088194 promotes RA-FLSs migration and invasion by increasing MMP2 expression.…”

Section: Resultsmentioning

confidence: 99%

Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis

et al. 2021

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Dysregulation of circular RNAs (circRNAs) is involved in various human diseases. Fibroblast-like synoviocytes (FLSs), which form the lining of the joint, are epigenetically imprinted with an aggressive phenotype and contribute to joint destruction in rheumatoid arthritis (RA). In the present study, we identified a novel circRNA, Circ_0088194, which was upregulated in RA fibroblast-like synoviocytes (RA-FLSs) and correlated with the disease activity score in 28 joints. Overexpression of Circ_0088194 promoted RA-FLS migration and invasion, while inhibition of Circ_0088194 had the opposite effect. Mechanistically, Circ_0088194 acted as a miR-766-3p sponge to relieve the repressive effect of miR-766-3p on its target, MMP2 (encoding matrix metalloproteinase 2), thereby promoting migration and invasion. The expression level of Circ_0088194 was inversely correlated with that of miR-766-3p in RA-FLSs. Importantly, overexpression of miR-766-3p partially blocked the migration and invasion induced by Circ_0088194 overexpression. Collectively, this study identified a novel circRNA Circ_0088194 that promotes RA-FLS invasion and migration via the miR-766-3p/MMP2 axis. Circ_0088194 might represent a novel therapeutic target to prevent and treat RA.

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Loss of SPINT2 expression frequently occurs in glioma, leading to increased growth and invasion via MMP2

Cited by 8 publications

References 54 publications

Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

Biomarkers, Master Regulators and Genomic Fabric Remodeling in a Case of Papillary Thyroid Carcinoma

Circ_0088194 Promotes the Invasion and Migration of Rheumatoid Arthritis Fibroblast-Like Synoviocytes via the miR-766-3p/MMP2 Axis

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