Oncogenicity of the transcription factor SOX8 in hepatocellular carcinoma

Zhang, Siquan; Zhu, Cong; Zhu, Limin; Liu, Huafeng; Liu, Shourong; Zhao, Nianbo; Wu, Jiang; Huang, Xiaoxiao; Zhang, Yujuan; Jin, Jie; Ji, Ting; Ding, Xiaohu

doi:10.1007/s12032-014-0918-3

Cited by 26 publications

(25 citation statements)

References 25 publications

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“…SOX8 is a regulator of the Wnt/β‐catenin signaling pathway, and consistent with this information, we observed reduced β‐catenin staining in both CAL27‐res and SCC9‐res shSOX8 cells compared to their corresponding parental cells. A decrease of C‐myc levels and an increase of Dkk1 levels were observed in chemoresistant cells infected shSOX8 compared to uninfected cells (Supporting Information Figs.…”

Section: Resultssupporting

confidence: 90%

“…29,30 Previous studies in hepatocellular carcinoma and gliomas have demonstrated that SOX8 promotes cell growth through the activation of Wnt/b-catenin signaling. 21,31 Xie et al also reported that SOX8, as a target of miR-124b, is overexpressed in lung cancer and closely associated with a poor prognosis. 32 In addition, we found that SOX8 expression correlated with lymph node metastasis rate and poor survival time in 103 TSCC patients and was higher especially in chemoresistant TSCC patients than in chemosensitive patients, indicating its potential value in chemoresistance.…”

Section: Disscussionmentioning

confidence: 99%

“…SOX8 belongs to the SOXE subfamily and is an important transcription factor that is mainly involved in regulating mammalian testis and nervous system development . Previous studies in hepatocellular carcinoma and gliomas have demonstrated that SOX8 promotes cell growth through the activation of Wnt/β‐catenin signaling . Xie et al .…”

Section: Disscussionmentioning

confidence: 99%

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SOX8 regulates cancer stem‐like properties and cisplatin‐induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β‐catenin pathway

Xie

Fan

Zhang

et al. 2017

Intl Journal of Cancer

114

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A sub-population of chemoresistant cells exhibits biological properties similar to cancer stem cells (CSCs), and these cells are believed to be a main cause for tumor relapse and metastasis. In our study, we explored the role of SOX8 and its molecular mechanism in the regulation of the stemness properties and the epithelial mesenchymal transition (EMT) of cisplatin-resistant tongue squamous cell carcinoma (TSCC) cells. We found that SOX8 was upregulated in cisplatin-resistant TSCC cells, which displayed CSC-like properties and exhibited EMT. SOX8 was also overexpressed in chemoresistant patients with TSCC and was associated with higher lymph node metastasis, advanced tumor stage and shorter overall survival. Stable knockdown of SOX8 in cisplatin-resistant TSCC cells inhibited chemoresistance, tumorsphere formation, and EMT. The Wnt/β-catenin pathway mediated the cancer stem-like properties in cisplatin-resistant TSCC cells. Further studies showed that the transfection of active β-catenin in SOX8 stable-knockdown cells partly rescued the SOX8 silencing-induced repression of stem-like features and chemoresistance. Through chromatin immunoprecipitation and luciferase assays, we observed that SOX8 bound to the promoter region of Frizzled-7 (FZD7) and induced the FZD7-mediated activation of the Wnt/β-catenin pathway. In summary, SOX8 confers chemoresistance and stemness properties and mediates EMT processes in chemoresistant TSCC via the FZD7-mediated Wnt/β-catenin pathway.

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Section: Resultssupporting

confidence: 90%

Section: Disscussionmentioning

confidence: 99%

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SOX8 regulates cancer stem‐like properties and cisplatin‐induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β‐catenin pathway

Xie

Fan

Zhang

et al. 2017

Intl Journal of Cancer

114

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“…Towards this goal, putative target genes of miR-139 were screened using bioinformatics methods. Among those genes, Sox8, belonging to group E of SOX family proteins, is reported to promote cell proliferation of diverse cancer cells [31, 32]. Several researchers have reported that Sox8 is expressed in the developing heart [33, 34].…”

Section: Discussionmentioning

confidence: 99%

Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139

Gong¹,

Xu²,

Guo³

et al. 2017

Cell Physiol Biochem

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Background/Aims: Acute myocardial infarction (AMI) occurs when blood supply to the heart is diminished (ischemia) for long time; ischemia is primarily caused due to hypoxia. The present study evaluated the effects of long non-coding RNA H19 on hypoxic rat H9c2 cells and mouse HL-1 cells. Methods: Hypoxic injury was confirmed by measuring cell viability, migration and invasion, and apoptosis using MTT, Transwell and flow cytometry assays, respectively. H19 expression after hypoxia was estimated by qRT-PCR. We then measured the effects of non-physiologically expressed H19, knockdown of miR-139 with or without H19 silence, and abnormally expressed Sox8 on hypoxia-induced H9c2 cells. Moreover, the interacted miRNA for H19 and downstream target gene were virtually screened and verified. The involved signaling pathways and the effects of abnormally expressed H19 on contractility of HL-1 cells were explored via Western blot analysis. Results: Hypoxia induced decreases of cell viability, migration and invasion, increase of cell apoptosis and up-regulation of H19. Knockdown of H19 increased hypoxia-induced injury in H9c2 cells. H19 acted as a sponge for miR-139 and H19 knockdown aggravated hypoxia-induced injury by up-regulating miR-139. Sox8 was identified as a target of miR-139, and its expression was negatively regulated by miR-139. The mechanistic studies revealed that overexpression of Sox8 might decrease hypoxia-induced cell injury by activating the PI3K/AKT/mTOR pathway and MAPK. Besides, H19 promoted contractility of HL-1 cells. Conclusion: These findings suggest that H19 alleviates hypoxia-induced myocardial cell injury by miR-139-mediated up-regulation of Sox8, along with activation of the PI3K/AKT/mTOR pathway and MAPK.

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“…There are few reports on soX8 in cancer. Zhang et al reported that soX8 promoted cancer cell proliferation in vitro and that its expression correlated with elevated β-catenin levels in hepatocellular carcinoma 90 .…”

Section: Mirnas Involved In Lymph Node Metastasismentioning

confidence: 99%

The role of microRNA in metastatic processes of non-small cell lung carcinoma

Pastorkova¹,

Škarda²,

Andel³

2016

BIOMED PAP

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Background. MicroRNAs are small non-coding one-stranded RNA molecules that play an important role in the posttranscriptional regulation of genes. Bioinformatic predictions indicate that each miRNA can regulate hundreds of target genes. MicroRNA expression can be associated with various cellular processes leading to the metastasis of malignant tumours including non-small cell lung carcinoma. This review summarizes current knowledge on the role of microRNAs in NSCLC metastasis to the brain and lymph nodes. Methods. A search of the NCBI/PubMed database for publications on expression levels and the mechanisms of microRNA action in NSCLC metastasis. Results and Conclusion. Dysregulation of microRNAs in NSCLC can be associated with brain and lymph node metastasis. There are differences in microRNA expression profiling between NSCLC with and without metastases but it is currently not possible to reliably predict the site of metastasis in NSCLC. Based on data from RNAmicroarrays, bioinformatics analysis is able to predict the target genes of highlighted microRNAs, providing us with complex information about cancer cell features such as enhanced proliferation, migration and invasion. Such microRNAs may then be knocked-down using siRNAs or substituted with miRNA mimics. RNA microarray profiling may thus be a useful tool to select up-or down-regulated microRNAs. A number of authors suggest that microRNAs could serve as biomarkers and therapeutic targets in the treatment of NSCLC metastasis.

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Oncogenicity of the transcription factor SOX8 in hepatocellular carcinoma

Cited by 26 publications

References 25 publications

SOX8 regulates cancer stem‐like properties and cisplatin‐induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β‐catenin pathway

SOX8 regulates cancer stem‐like properties and cisplatin‐induced EMT in tongue squamous cell carcinoma by acting on the Wnt/β‐catenin pathway

Long Non-Coding RNA H19 Protects H9c2 Cells against Hypoxia-Induced Injury by Targeting MicroRNA-139

The role of microRNA in metastatic processes of non-small cell lung carcinoma

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