SOX9: Advances in Gynecological Malignancies

Chen, Huan; He, Yujie; Wen, Xiangping; Shao, Shihong; Liu, Yujie; Wang, Jinjin

doi:10.3389/fonc.2021.768264

Cited by 6 publications

(4 citation statements)

References 91 publications

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“…Our study not only highlights DYRK3 as a tumor-promoting oncogene in SOC but also elucidates its potential as a therapeutic target by demonstrating the inhibitory effects of DYRK3 knockdown on cell viability, invasion, and in vivo tumor growth. By analyzing the correlation between DYRK3 and EMT-related genes [ 8 ] in TCGA-ovarian cancer dataset, we observed a positive correlation between DYRK3 with FLNB and SOX9, both of which had been well acknowledged as oncogenic molecules in tumorigenesis and cancer progression [ 10 – 13 ]. We also found that knockdown of DYRK3 can downregulate the protein expression of filamin B and SOX9.…”

Section: Discussionmentioning

confidence: 99%

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 3 Expression and Its Correlation with Prognosis and Growth of Serous Ovarian Cancer: Correlation of DYRK3 with Ovarian Cancer Survival

Sun,

Zhang,

et al. 2024

International Journal of Genomics

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Background. Epithelial ovarian cancer, primarily serous ovarian cancer (SOC), stands as a predominant cause of cancer-related mortality among women globally, emphasizing the urgent need for comprehensive research into its molecular underpinnings. Within this context, the dual-specificity tyrosine phosphorylation-regulated kinase 3 (DYRK3) has emerged as a potential key player with implications for prognosis and tumor progression. Methods. This study conducted a meticulous retrospective analysis of 254 SOC cases from our medical center to unravel the prognostic significance of DYRK3. Survival analyses underscored DYRK3 as an independent adverse prognostic factor in SOC, with a hazard ratio of 2.60 (95% CI 1.67-4.07, P<0.001). Experimental investigations involved DYRK3 knockdown in serous ovarian cancer cell lines (CAOV3 and OVCAR-3) through a shRNA strategy, revealing substantial decreases in cell growth and invasion capabilities. Bioinformatics analyses further hinted at DYRK3’s involvement in modulating the tumor immune microenvironment. In vivo experiments with DYRK3-knockdown cell lines validated these findings, demonstrating a notable restriction in the growth of ovarian cancer xenografts. Results. Our findings collectively illuminate DYRK3 as a pivotal tumor-promoting oncogene in SOC. Beyond its adverse prognostic implications, DYRK3 knockdown exhibited promising therapeutic potential by impeding cancer progression and potentially influencing the tumor immune microenvironment. Conclusions. This study establishes a compelling foundation for further research into DYRK3’s intricate role and therapeutic potential in ovarian cancer treatment. As we unravel the complexities surrounding DYRK3, our work not only contributes to the understanding of SOC pathogenesis but also unveils new prospects for targeted therapeutic interventions, holding promise for improved outcomes in ovarian cancer management.

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Section: Discussionmentioning

confidence: 99%

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 3 Expression and Its Correlation with Prognosis and Growth of Serous Ovarian Cancer: Correlation of DYRK3 with Ovarian Cancer Survival

Sun,

Zhang,

et al. 2024

International Journal of Genomics

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“…In endometrial cancer, upregulation of SOX9 could promote endometrial cell proliferation, induce endometrial precancerous lesions, and predict the prognosis of endometrial cancer patients in combination with the expression of other genes. In uterine sarcoma, upregulation of SOX9 promotes epithelial-mesenchymal transition, leading to sarcoma formation ( Chen et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…SOX9 also plays an important role in other types of gynecological malignancies. In ovarian epithelial tumors, many studies have found that SOX9 is significantly higher in tumor tissue than in normal ovarian tissue, and its expression correlates with overall survival and progressionfree survival of ovarian cancer patients; elevated expression of some miRNAs can suppress SOX9 expression, thereby Frontiers in Genetics frontiersin.org inhibiting ovarian cancer cell growth and multicellular spheroids formation; ceRNA network-regulated SOX9 expression is involved in the development of ovarian cancer, maintenance of tumor stem cell properties, antiapoptosis, migration, and invasion; meanwhile, SOX9 expression is associated with chemoresistance resistance in ovarian cancer patients (Chen et al, 2021). Recent studies have also demonstrated that cytoplasmic SOX9-mediated cell death inhibition contributes to the survival of cancer stem cells in high-grade ovarian cancer (Oh et al, 2022).…”

Section: Figurementioning

confidence: 99%

Prognostic value of SOX9 in cervical cancer: Bioinformatics and experimental approaches

Chen

Zeng

et al. 2022

Front. Genet.

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Among gynecological cancers, cervical cancer is a common malignancy and remains the leading cause of cancer-related death for women. However, the exact molecular pathogenesis of cervical cancer is not known. Hence, understanding the molecular mechanisms underlying cervical cancer pathogenesis will aid in the development of effective treatment modalities. In this research, we attempted to discern candidate biomarkers for cervical cancer by using multiple bioinformatics approaches. First, we performed differential expression analysis based on cervical squamous cell carcinoma and endocervical adenocarcinoma data from The Cancer Genome Atlas database, then used differentially expressed genes for weighted gene co-expression network construction to find the most relevant gene module for cervical cancer. Next, the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed on the module genes, followed by using protein–protein interaction network analysis and Cytoscape to find the key gene. Finally, we validated the key gene by using multiple online sites and experimental methods. Through weighted gene co-expression network analysis, we found the turquoise module was the highest correlated module with cervical cancer diagnosis. The biological process of the module genes focused on cell proliferation, cell adhesion, and protein binding processes, while the Kyoto Encyclopedia of Genes and Genomes pathway of the module significantly enriched pathways related to cancer and cell circle. Among the module genes, SOX9 was identified as the hub gene, and its expression was associated with cervical cancer prognosis. We found the expression of SOX9 correlates with cancer-associated fibroblast immune infiltration in immune cells by Timer2.0. Furthermore, cancer-associated fibroblast infiltration is linked to cervical cancer patients’ prognosis. Compared to those in normal adjacent, immunohistochemical and real-time quantitative polymerase chain reaction (qPCR) showed that the protein and mRNA expression of SOX9 in cervical cancer were higher. Therefore, the SOX9 gene acts as an oncogene in cervical cancer, interactive with immune infiltration of cancer-associated fibroblasts, thereby affecting the prognosis of patients with cervical cancer.

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“…Up to now, the obscurity of the molecular mechanisms related to the incidence and development of gynecological malignancies has been the main theme of the studies. Recent studies have reported that multiple mechanisms play a role in the regulation of the expression of the sex-determining region Y-box 9, which leads to the emergence and development of gynecological malignancies 10 . In addition, members of the SOX family contain a conserved high mobility group DNA binding domain.…”

Section: Introductionmentioning

confidence: 99%

Role of SOX9 and Hif-1α expression in placentas of patients with HELLP

Akalın,

Öcal,

Deveci

2023

Acta Cir. Bras.

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Purpose: In this study, we investigated the immunohistochemical staining of SRY-box transcription factor 9 (SOX9) and Hif-1α expression in placentas of pregnant woman with hemolysis, elevated liver enzymes and low platelets (HELLP) syndrome. Methods: Placentas of 20 normotensive and 20 women with HELLP syndrome were processed for routine histological tissue processing. The biochemical and clinical parameters of patients were recorded. Placentas were stained with hematoxylin-eosin and SOX9 and Hif-1α immunostaining. Results: Normotensive placentas showed normal histology of placenta, however placentas of HELLP syndrome showed intense thrombosis, thinning of the villi membrane and vascular dilatation. In placentas of normotensive patients, SOX9 reaction was immunohistochemically negative, however placentas of HELLP group showed SOX9 expression in decidual cells, and syncytial regions of floating villi and inflammatory cells. In placentas of normotensive patients, Hif-1α reaction was mainly negative in vessels and connective tissue cells. Placentas of HELLP group showed increased Hif-1α expression in decidual cell and especially inflammatory cells in the maternal region. Conclusions: Hif-1α and SOX9 proteins can be used as a marker to show severity of preeclampsia and regulation of cell proliferation and angiogenesis during placental development.

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SOX9: Advances in Gynecological Malignancies

Cited by 6 publications

References 91 publications

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 3 Expression and Its Correlation with Prognosis and Growth of Serous Ovarian Cancer: Correlation of DYRK3 with Ovarian Cancer Survival

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 3 Expression and Its Correlation with Prognosis and Growth of Serous Ovarian Cancer: Correlation of DYRK3 with Ovarian Cancer Survival

Prognostic value of SOX9 in cervical cancer: Bioinformatics and experimental approaches

Role of SOX9 and Hif-1α expression in placentas of patients with HELLP

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