SOX9: An emerging driving factor from cancer progression to drug resistance

Panda, Munmun; Tripathi, Surya Kant; Biswal, Bijesh K.

doi:10.1016/j.bbcan.2021.188517

Cited by 50 publications

(34 citation statements)

References 169 publications

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“…As a transcription factor, SOX9 has been implicated in the initiation, development, and progression of tumors in multiple organs (15). However, the role of SOX9 in TETs has not been reported yet.…”

Section: Discussionmentioning

confidence: 99%

“…Accumulating studies have demonstrated that SOX9 is also involved in the development of multiple cancers, including gastrointestinal, breast, brain, urological, and lung cancers and others (9)(10)(11)(12)(13). Collectively, SOX9 plays critical roles in tumor development and progression, including tumor initiation, tumor microenvironment regulation, metastasis, and drug resistance (14,15).…”

Section: Introductionmentioning

confidence: 99%

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Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor

et al. 2021

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BackgroundThymic epithelial tumors (TETs) are rare tumors originating from the thymic epithelial cells. SOX9, a member of the family of SOX (SRY-related high-mobility group box) genes, has been considered as an oncogene and therapeutic target in various cancers. However, its role in TETs remains uncertain.MethodsUsing the immunohistochemistry method, the expression of SOX9 was analyzed in TETs tissues, including 34 thymoma (8 cases with type A, 6 with type AB, 6 with type B1, 9 with type B2, and 5 with type B3 thymomas) and 20 thymic cancer tissues and the clinicopathologic and prognostic significances were evaluated. Further bioinformatics analysis of gene expression profiles of thymomas with high and low SOX9 expressions and the corresponding survival analyses were based on the thymoma cases identified in The Cancer Genome Atlas (TCGA) database, with the median expression level of SOX9 selected as cutoff.ResultsImmunohistochemistry staining showed that SOX9 was highly expressed in the nuclei of the epithelial cells of the Hassall’s corpuscles and of the TET tumor cells. SOX9 expression was significantly associated with histological type and high expression indicated unfavorable clinical outcomes of thymomas. Bioinformatics analysis revealed that genes positively associated with SOX9 expression were mapped in proteoglycans in cancer, cell adhesion molecules, and molecules involved in extracellular matrix-receptor interaction and the TGF-β signaling pathway, and that genes negatively associated with SOX9 expression were mapped in molecules involved in primary immunodeficiency, the T cell receptor signaling pathway, Th17 cell differentiation, PD-L1 expression, and the PD-1 checkpoint pathway in cancer. In addition, SOX9 expression was positively associated with POU2F3 and TRPM5 expressions, the master regulators of tuft cells, suggesting that high SOX9 expression might be associated with the tuft cell phenotype of thymomas. Moreover, high SOX9 expression was associated with immune dysregulation of thymoma, and M2 macrophage significantly dominated in the high SOX9 expression group.ConclusionSOX9 may serve as a diagnostic and prognostic marker for TETs. Notably, high SOX9 expression in TETs may indicate a tuft cell phenotype and an immune suppressive microenvironment of thymomas.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor

et al. 2021

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“…5 g and h). Both c-Myc and SOX9 were reported to play essential roles in normal cells and frequently dysregulated in human cancers [ 48 – 50 ]. For example, c-Myc and SOX9 were remarkably upregulated in the colorectal cancer and can accelerate cell proliferation [ 48 , 51 ].…”

Section: Discussionmentioning

confidence: 99%

Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing

Zeng

Wang

et al. 2021

Mol Cancer

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Background Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown. Methods In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays. Results We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer β-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation. Conclusions Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of β-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.

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“…Our results suggested that the level of miRNA-216b in patients may be used for the early detection of NSCLC as well as for differentiating between early and advanced cancer. Studies had shown that miRNA-216b can inhibit the proliferation and invasion of NSCLC cells by directly targeting the 3′ untranslated region and negatively regulating the expression of SOX9, which was an oncogene regulated by multiple miRNAs in various types of human cancer [ 58 ]. In addition, the upregulation of miRNA-216b expression was related to the histological stage of NSCLC, and patients with lower miRNA-216b levels had a shorter survival time [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

The expression of miRNA-216b is negatively correlated with 18F-FDG uptake in non-small cell lung cancer

et al. 2021

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Background This study aimed to investigate the correlation between miRNA-216b expression in patients with non-small cell lung cancer (NSCLC) and 18F-fluorodeoxyglucose (FDG) uptake by PET/CT and to explore the clinical application value of 18F-FDG PET/CT in miRNA-216b based on therapy for NSCLC. Methods Eighty patients with NSCLC and 40 healthy subjects were enrolled in our study. The SUVmax of the lesion area by PET/CT imaging was calculated. SUVmax represented the highest concentration of 18F-FDG in the lesion. The expression of miRNA-216b in the plasma and fiber bronchoscopic puncture of NSCLC patients was detected by RT qPCR. Then Pearson correlation analysis was used to analyze the correlation between miRNA-216b expression and 18F-FDG uptake in patients with different types of NSCLC. Results Compared with healthy subjects, SUVmax of early adenocarcinoma and advanced adenocarcinoma were increased. Compared with healthy subjects, SUVmax of early squamous and advanced squamous were increased. And the SUVmax content of advanced adenocarcinoma and squamous cell carcinoma was higher than that of early adenocarcinoma and squamous cell carcinoma. Compared with healthy subjects, the expression of miRNA-216b in the plasma of patients with early and advanced adenocarcinoma was reduced, and the expression of miRNA-216b in the plasma of patients with early and advanced squamous cell carcinoma was reduced. Compared with adjacent tissues, the expression of miRNA-216b in early adenocarcinoma tissues and advanced adenocarcinoma tissues was reduced, and the expression in early squamous cell carcinoma and advanced squamous cell carcinoma was reduced. Pearson correlation analysis showed a negative correlation between SUVmax and miRNA-216b (plasma and tissue) in patients with four types of NSCLC. Conclusion miRNA-216b expression was negatively correlated with 18F-FDG uptake in NSCLC. miRNA-216b could be used for the classification and staging of non-small cell lung cancer. 18F-FDG PET/CT may be used to evaluate the therapeutic response in application of miRNA-216b-based cancer treatment.

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SOX9: An emerging driving factor from cancer progression to drug resistance

Cited by 50 publications

References 169 publications

Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor

Diagnostic and Prognostic Significances of SOX9 in Thymic Epithelial Tumor

Characterization of novel CTNNB1 mutation in Craniopharyngioma by whole-genome sequencing

The expression of miRNA-216b is negatively correlated with 18F-FDG uptake in non-small cell lung cancer

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