Upregulation of sex-determining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma

Yun, Hong Shik; Chen, Wen; Du, Xiao‐Jun; Ning, Huiwen; Chen, Huaisheng; Shi, Ruiqing; Lin, Shaolin; Xu, Rui‐hua; Zhu, Jinrong; Wu, Shu; Zhou, Haiyu

doi:10.18632/oncotarget.5160

Cited by 37 publications

(37 citation statements)

References 42 publications

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“…The exact role of SOX9 in carcinogenesis and cancer progression is controversial because both oncogenic and tumor-suppressing functions of SOX9 have been described (Passeron et al 2009;Cai et al 2013;. Furthermore, SOX9 expression is up-regulated in several tumor types, including lung adenocarcinoma, esophageal squamous cell carcinoma and breast cancer (Müller et al 2010;Hong et al 2015;Wang et al 2015). It has been demonstrated that expression levels of SOX9 mRNA and protein are significantly higher in osteosarcoma tissues (Zhu et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Yang

Hao

et al. 2017

Tohoku J. Exp. Med.

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Osteosarcoma is a malignant bone cancer that mainly affects children. SOX9 plays a key role in bone formation and osteosarcoma, and Claudin-8 (CLDN8), a tight junction protein, contributes to proliferation of osteosarcoma cells. The aim of this study was to investigate the relationship between SOX9 and CLDN8 in osteosarcoma. The expression levels of SOX9 and CLDN8 were determined in osteosarcoma specimens (n = 25) by qRT-PCR and Western blot analyses. The levels of SOX9 mRNA and protein were significantly higher in osteosarcoma tissues than those in adjacent non-tumor tissues, whereas the expression levels of CLDN8 mRNA and protein were significantly lower in osteosarcoma tissues. Immunohistochemical analysis showed the high expression of SOX9 in 56 out of 97 osteosarcoma tissues (57.7%). By contrast, the low expression of immunoreactive CLDN8 was observed in 62 of 97 osteosarcoma tissues (63.9%). There was the inverse correlation between the expression levels of SOX9 and CLDN8 proteins (R = −0.633, P < 0.001). The overall survival was poorer in the patients with high SOX9 expression. Subsequently, using two human osteosarcoma cell lines, we showed that knockdown of SOX9 inhibited cell proliferation and migration but promoted cell apoptosis. Importantly, knockdown of SOX9 increased the expression levels of CLDN8 protein. The transient luciferase-reporter assays suggest that SOX9 may inhibit the promoter activity of the CLDN8 gene in osteosarcoma cells. In conclusion, we provide the evidence demonstrating that SOX9 may promote cell growth by repressing the expression of CLDN8. Thus, SOX9 may be a therapeutic target for osteosarcoma.

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Section: Introductionmentioning

confidence: 99%

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Yang

Hao

et al. 2017

Tohoku J. Exp. Med.

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“…According to our analysis, these miRNAs play critical roles in several cellular and molecular processes. (Hong et al, 2015). Wang in 2012 reported that the miR-196a binding-site SNP regulates RAP1A expression contributing to ESCC risk and metastasis (K. Wang et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

In silico evidence of high frequency of miRNA‐related SNPs in Esophageal Squamous Cell Carcinoma

Rafieenia

Abbaszadegan

Poursheikhani

et al. 2019

Journal Cellular Physiology

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Esophageal squamous cell carcinoma (ESCC) is the dominant histological type of esophageal cancer significantly reported in developing nations. There is an increasing evidence suggesting that single nucleotide polymorphisms (SNPs) in the untranslated regions of genes (3′-UTRs) targeted by microRNAs (miRNAs) can change the target gene's expression and thereby affect the individual's cancer risk. Thus, in support of the role of SNPs occurring in miRNA target sites (miR-TS-SNPs) in the cancer, we analyzed the next generation sequencing data of 10 ESCC patients. In each patient, about 3,000 SNPs in 3′-UTRs were obtained in their whole-exome sequencing profiles. We applied two separate methods, manual and computational in silico approaches, to predict the miR-TS-SNPs with more effects on the miRNA-target interactions. dbSNP, 1000G, ExAC, Iranome, miRandb, miRCancer, TargetScan, Human, miRNASNP2 and miRBase databases were used for positive selection of miR-TS-SNPs and DIANA-miRPath v3.0 for pathway analysis. We identified six rare germline miR-TS-SNPs and two other ones with unknown miR-TS-SNPs. We interestingly observed all of these variants in only one patient, which can be evidence of the relationship between miR-TS-SNPs and cancer incidence. The study of cancer genetics including miR-TS-SNPs reveals miRNAs and their related pathways, which will be greatly useful in cancer research from noninvasive biomarkers to new treatments. K E Y W O R D SESCC, in silico analysis, miR-TS-SNPs, NGS

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“…For example, p-Akt promotes cell proliferation and survival in vitro and serves an important function in prostate cancer progression, as well as the prediction of recurrence (20), and decreased expression of p-Akt inhibits polydatin-induced cell proliferation and induces apoptosis in laryngeal cancer and HeLa cells (21). Furthermore, overexpression of p-Akt promotes the proliferation and tumorigenesis of the esophageal cancer cell line ECA-109 (22). Therefore, miR302a may have targeted p-ERK1/2 and p-Akt through the MAPK and PI3K signaling pathways, respectively, and this may be its primary contribution to the inhibition of cell proliferation in TE-10 and ECA109 cells.…”

Section: Discussionmentioning

confidence: 99%

miR302a inhibits the proliferation of esophageal cancer cells through the MAPK and PI3K/Akt signaling pathways

et al. 2018

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Abstract. MicroRNAs (miRNAs/miRs) are involved in the regulation of various types of cancer, either as oncogenes or tumor suppressors. miR302a has been reported that it could suppress tumor cell proliferation by inhibiting Akt in prostate cancer. The present study examined the effect of miR302a on proliferation and invasion in esophageal cancer cell lines. The expression levels of miR302a in esophageal cancer cell lines was determined by reverse transcription-polymerase chain reaction. Subsequently, miR302a mimics were transfected into esophageal cancer cells, and cell viability and invasion were assessed by MTT and Transwell assays. In addition, the effects of miR302a on the mitogen-activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathways were investigated by western blot analysis. The results revealed that miR302a expression was significantly decreased in the esophageal cancer cell lines compared with a healthy esophagus epithelium cell line. Upregulation of miR302a inhibited the proliferation and invasion of esophageal cancer cells, and decreased the phosphorylation of extracellular signal-regulated kinase 1/2 and Akt. Taken together, the results of the present study indicated that miR302a overexpression inhibited the proliferation and invasion of esophageal cancer cells through suppression of the MAPK and PI3K/Akt signaling pathways, indicating the potential value of miR302a as a treatment target for human esophageal cancer.

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Upregulation of sex-determining region Y-box 9 (SOX9) promotes cell proliferation and tumorigenicity in esophageal squamous cell carcinoma

Cited by 37 publications

References 42 publications

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

Transcription Factor SOX9 Promotes Osteosarcoma Cell Growth by Repressing Claudin-8 Expression [Retraction]

In silico evidence of high frequency of miRNA‐related SNPs in Esophageal Squamous Cell Carcinoma

miR302a inhibits the proliferation of esophageal cancer cells through the MAPK and PI3K/Akt signaling pathways

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