Down-regulation of SOX18 inhibits laryngeal carcinoma cell proliferation, migration, and invasion through JAK2/STAT3 signaling

Xu, Yice; Zhang, Qingyuan; Zhou, Jie; Li, Zhaolong; Guo, Junyu; Wang, Weina; Wang, Wei

doi:10.1042/bsr20182480

Cited by 9 publications

(5 citation statements)

References 24 publications

(23 reference statements)

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“…The JAK2/STAT3 pathway is participated in the progression of lymphangiogenesis, and SOX18 has been reported to regulate this pathway [ 25 ]. Therefore, we investigated whether SOX18-mediated JAK2/STAT3 activation was involved in lymphangiogenesis.…”

Section: Resultsmentioning

confidence: 99%

“…IL-6 has been also showed to promote lymphangiogenesis via activation of the JAK/STAT3 signaling [ 39 , 40 ]. SOX18 has been showed to regulate the JAK2/STAT3 pathway to promote laryngeal carcinoma cell growth, cell motility, and invasion [ 25 ]. Consistently, we found that the ectopic experssion of SOX18 increased the phosphorylation of JAK2 and STAT3.…”

Section: Discussionmentioning

confidence: 99%

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EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway

Yang

et al. 2022

Computational and Mathematical Methods in Medicine

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Background. Lymphangiogenesis is a process involved in the pathogenesis of many diseases. Identifying key molecules and pathway targeting this process is critical for lymphatic regeneration-associated disorders. EGR1 is a transcription factor, but its function in lymphangiogenesis is not yet known. This study is aimed at exploring the functional activity and molecular mechanism of EGR1 implicated in lymphangiogenesis. Methods. The CCK-8 method, transwell migration assay, and tube formation assay were used to detect the cell viability, motility, and tube formation of HDLEC cells, respectively. The luciferase reporter assay was applied to detect the impact of EGR1 on SOX18 promoter activity. CHIP assay was used to analyze the direct binding of EGR1 to the SOX18 promoter. qRT-PCR and Western blot analysis were performed to investigate molecules and pathway involved in lymphangiogenesis. Results. The EGR1 ectopic expression markedly increased the cell growth, mobility, tube formation, and the expression of lymphangiogenesis-associated markers (LYVE-1 and PROX1) in HDLEC cells. EGR1 interacted with the SXO18 gene promoter and transcriptionally regulated the SXO18 expression in HDLEC cells. Silencing of SOX18 abrogated the promotional activities of EGR1 on the cell viability, mobility, tube formation, and LYVE-1/PROX1 expression in HDLEC cells. SOX18 overexpression activated JAK/STAT signaling, which resulted in an increase in lymphangiogenesis in HDLEC cells. Conclusions. ERG1 can promote lymphangiogenesis, which is mediated by activating the SOX18/JAK/STAT3 cascade. ERG1 may serve as a promising target for the therapy of lymphatic vessel-related disorders.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway

Yang

et al. 2022

Computational and Mathematical Methods in Medicine

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“…This finding is in agreement with Ma et al ., 15 who concluded that high expression of SOX18 might be a predictive marker of bad prognostic types of esophageal SCC. Furthermore, Xu et al ., 16 demonstrated that SOX18 was overexpressed in laryngeal SCC, and its expression correlated with poor outcome.…”

Section: Discussionmentioning

confidence: 99%

“…Francois et al ., 6 reported that SOX18 is essential for stimulation of the prospero homeobox 1 promoter that is required for the development of new blood and lymphatic vessels in tumor evolution and metastasis. Furthermore, Xu et al ., 16 concluded that SOX18 regulated the cell proliferation, cell cycle, apoptosis, migration, and invasion of tumor cells via JAK2/STAT3 signaling.…”

Section: Discussionmentioning

confidence: 99%

Significance of SOX18 expression in nonmelanoma skin cancers for prediction of high‐risk patients: a preliminary study

et al. 2020

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Background SOX18 is an integral transcription factor that is involved in endothelial cells differentiation during both angiogenesis and lymphangiogenesis. Therefore, it has been implicated in tumor progression and metastasis. Objective To study SOX18 expression in nonmelanoma skin cancers (NMSCs) in comparison to seborrheic keratosis (SK) and normal control skin, and to assess its probable role in tumor evolution and progression. Patients and Methods This study was conducted on 60 specimens of NMSCs: 30 basal cell carcinomas (BCC) and 30 squamous cell carcinomas (SCC), 30 specimens of SK, and 30 normal skin specimens. All were examined for immunohistochemical expression of SOX18 antibody. Additionally, morphometric assessment of vessel density (blood & lymphatic) in each specimen was estimated. Results Significant SOX18 overexpression was observed in all studied cutaneous tumors in comparison to control skin. The highest score of SOX18 expression was detected in SCC, then BCC, and the least expression was reported in SK with significant difference between them. Furthermore, significant upregulation of SOX18 expression was observed in high‐risk types of both BCC and SCC compared to low‐risk types. Stromal vessel density showed significant differences between the studied tumors with the highest mean value in SCC, followed by BCC and then SK. Positive correlation between SOX18 expression in the studied tumors and their vessel density was detected. Conclusions SOX18 may have a potential role in the evolution as well as progression of NMSCs, possibly through induction of both angiogenesis and lymphangiogenesis. Furthermore, it could be beneficial for prediction of NMSC patients with poor prognosis.

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“…A large amount of ROS produced during apoptosis is derived from mitochondria, and the increase in ROS is directly related to apoptosis (18). Moreover, according to a study of Xu et al (19), lowering the phosphorylation level of STAT3 can effectively reduce the mitochondrial membrane potential, increase the content of ROS in cells, and induce mitochondrial apoptosis. In the present study, the results revealed that downregulation of miR-19a expression in osteosarcoma cells markedly increased the content of ROS in cells, suppressed the JAK2/STAT3 signaling pathway in cells, and markedly reduced the expression levels of p-JAK2, p-STAT3 and anti-apoptotic protein Mcl-1.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of miR‑19a inhibits the proliferation and promotes the apoptosis of osteosarcoma cells by regulating the JAK2/STAT3 pathway

Chen

2020

Oncol Lett

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Osteosarcoma is a malignant tumor derived from the skeletal system, often occurring in bone tissues, and it is the most common malignant tumor in the skeletal system, with more than 90% of cases being highly malignant. The present study was designed to explore the regulatory effects of microRNA (miR)-19a on the proliferation and apoptosis of osteosarcoma cells, and its influence on the activation of the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling pathway. The expression of miR-19a in adult SaOS-2 osteosarcoma cells was downregulated via lentiviral transfection, and the cells were divided into a control group, NC-inhibitor group and miR-19a-inhibitor group. The expression of miR-19a in each group was detected via quantitative polymerase Chain reaction (qPCR). Next, the cell proliferation and apoptosis levels in each group were detected via methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively, and the level of reactive oxygen species (ROS) in cells was further determined. Moreover, the expression levels of apoptosis-related proteins and JAK2/STAT3 signaling pathway-related proteins were detected through western blotting. The expression level of miR-19a in the miR-19a-inhibitor group was significantly lower than that in the control group and NC-inhibitor group (P<0.01). Downregulation of miR-19a significantly reduced the proliferation ability (P<0.01), increased the apoptosis level of SaOS-2 cells (P<0.01), and significantly increased the ROS level in cells (P<0.01). Downregulation of miR-19a also promote cleaved caspase-3/caspase-3 expression in the OS cells (P<0.01) and inhibited Bcl-2/Bax expression (P<0.01). Additionally, downregulation of miR-19a markedly lowered the protein expression levels of phosphorylated (p-)JAK2, p-STAT3 and myeloid cell leukemia-1 (Mcl-1) in the cells (P<0.01). To conclude, downregulation of miR-19a can inhibit the JAK2/STAT3 signaling pathway in SaOS-2 cells, promote the expression of apoptosis-related proteins, and increase the ROS level in cells, thereby promoting apoptosis and inhibiting cell proliferation.

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Down-regulation of SOX18 inhibits laryngeal carcinoma cell proliferation, migration, and invasion through JAK2/STAT3 signaling

Cited by 9 publications

References 24 publications

EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway

EGR1 Enhances Lymphangiogenesis via SOX18-Mediated Activation of JAK2/STAT3 Pathway

Significance of SOX18 expression in nonmelanoma skin cancers for prediction of high‐risk patients: a preliminary study

Downregulation of miR‑19a inhibits the proliferation and promotes the apoptosis of osteosarcoma cells by regulating the JAK2/STAT3 pathway

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