Expression of SOX9 Is Related to Prognosis in Patients with Oesophageal Squamous Cell Carcinoma

Higo, Naotomo; Okumura, Hiroshi; Uchikado, Yasuto; Omoto, Itaru; Sasaki, Ken; Kita, Yoshiaki; Desaki, Ryosuke; Noda, Masahiro; Owaki, Tetsuhiro; Ishigami, Sumiya; Natsugoe, Shoji

doi:10.21873/invivo.11316

Cited by 8 publications

(3 citation statements)

References 13 publications

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“…SOX9, a member of the sex-determining region Y box family, was validated to be a direct target of miR-605 in GBM. SOX9 is overexpressed in various types of human malignant tumors, including hepatocellular carcinoma,36 thyroid cancer,37 gastric cancer,38 esophageal squamous cell carcinoma,39 and non-small cell lung cancer 40. Expression of SOX9 is also increased in GBM cells, and the increase of SOX9 expression is significantly associated with WHO grade and KPS 24.…”

Section: Discussionmentioning

confidence: 99%

<p>microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway</p>

Jia

Wang

Yin

et al. 2019

OTT

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Background Aberrant microRNA (miRNA) expression has been widely reported to play a crucial role in the progression and development of glioblastoma (GBM). miR-605 has been identified as a tumor-suppressing miRNA in several types of human cancers. Nevertheless, the expression profile and detailed roles of miR-605 in GBM remain unclear and need to be further elucidated. Materials and methods RT-qPCR analysis was utilized for the determination of miR-605 expression in GBM tissues and cell lines. In addition, CCK-8 assay, transwell migration and invasion assays, as well as sub-cutaneous xenograft mouse models were utilized to evaluate the effects of miR-605 upregulation in GBM cells. Notably, the potential mechanisms underlying the activity of miR-605 in the malignant phenotypes of GBM were explored. Results We observed that expression of miR-605 was reduced in GBM tissues and cell lines. Decreased miR-605 expression exhibited significant correlation with KPS score. The overall survival rate in GBM patients with low miR-605 expression was lower than that of patients with high miR-605 expression. Increased miR-605 expression suppressed the proliferation, migration, and invasion of U251 and T98 cells. In addition, miR-605 upregulation impaired tumor growth in vivo. Furthermore, SRY-Box 9 (SOX9) was identified as a direct target gene of miR-605 in U251 and T98 cells. SOX9 expression was shown to exhibit an inverse correlation with miR-605 expression in GBM tissues. Moreover, silencing of SOX9 expression mimicked the tumor-suppressing roles of miR-605 in U251 and T98 cells, while SOX9 restoration rescued the suppressive effects of miR-605 overexpression in the same. Notably, miR-605 suppressed the PI3K/Akt pathway in GBM in vitro and in vivo. Conclusion These results demonstrated that miR-605 acts as a tumor suppressor in the development of GBM by directly targeting SOX9 and inhibiting the activation of the PI3K/Akt pathway, suggesting its potential role as a therapeutic target for GBM.

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Section: Discussionmentioning

confidence: 99%

<p>microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway</p>

Jia

Wang

Yin

et al. 2019

OTT

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“…Our model, comprising genes such as HHIPL2, SOX9, DDX11, WNT7A, WNT10B, GNG7, SIX1, FZD3, PABPC1, FOXM1, ALDOA, CEP55, INTS7, FADD, CDC25C, CD69, EPHB2, and PTGIS, was validated across multiple cohorts. Several of these genes have been previously investigated: HHIPL2 is differentially expressed in gastric cancer tissues [34], SOX9 is associated with the prognosis of esophageal and oral squamous cell carcinoma [35,36], and DDX11 may have an oncogenic role [37]. Additionally, Wnt7A is secreted by aggressive breast tumor cells [38], and WNT10B is critical for gastric cancer progression [39].…”

Section: Discussionmentioning

confidence: 99%

Constructing and identifying an eighteen-gene Tumor Microenvironment Prognostic Model for Non-Small Cell Lung Cancer

Li,

Meng,

Xiao

et al. 2024

Preprint

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Background The tumor microenvironment (TME) plays a crucial role in tumorigenesis and tumor progression. This study aimed to identify novel TME-related biomarkers and develop a prognostic model for patients with non-small-cell lung cancer (NSCLC). Methods After downloading and preprocessing data, we classified the molecular subtypes using the "NMF" R package. We performed survival analysis and quantified immune scores between clusters. A Cox proportional hazards model was then constructed, and its formula was produced. We assessed model performance and clinical utility. A prediction nomogram was also constructed and validated. Additionally, we explored the potential regulatory mechanisms of our TME gene signature using Gene Set Enrichment Analysis (GSEA). Results From data processing and univariate Cox regression, 57 TME-related prognostic genes were identified. Two clusters (C1 and C2) with significant differences were established. Immune scores, including those for cytotoxic lymphocytes, endothelial cells, monocytic cells, myeloid dendritic cells, neutrophils, and T cells, showed significant differences between the subtypes. Through univariate Cox analysis, lasso regression, and multivariate Cox regression analysis, an 18-gene TME-related prognostic model was developed. This model accurately predicted survival outcomes in subgroups with varying clinical features. Finally, a nomogram was constructed, and its predictive accuracy was validated. Conclusions We developed a prognostic model based on TME-related genes in NSCLC. Our 18-gene TME signature can effectively predict the prognosis of NSCLC with high accuracy.

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“…The transcription factor SOX9 plays a vital role in embryonic development and is highly expressed in various tumors, such as prostate, non-small cell lung, and breast cancers [6][7][8]. Overexpression of SOX9 in cancers is associated with the regulation of cell proliferation and metastasis [9]. Furthermore, SOX9 has been related to tumorigenesis through the Hippo-YAP signaling pathway regulating tissue homeostasis and stem cell self-renewal.…”

Section: Introductionmentioning

confidence: 99%

Subcellular localization of HMGB1 in human cholangiocarcinoma: correlation with tumor stage

Suwannakul

Midorikawa

et al. 2021

Discov Onc

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Cholangiocarcinoma (CCA) is a malignant disease with a poor prognosis, and several studies have been conducted using different molecular markers as a tool for CCA diagnosis, including Clonorchis sinensis (CS)-CCA. We initially identified the expression profiles of the three markers of interest, HMGB1, SOX9, and YAP1, using GSE (GSE76297 and GSE32958) datasets. Upregulated levels of these three proteins were detected in CCA samples compared to those in normal samples. To clarify this issue, 24 human CCA tissues with paired adjacent normal tissues were evaluated using immunohistochemical staining. Of the three markers, the total cellular staining intensities were scanned, and subcellular localization was scored in the nuclear and cytoplasmic regions. The intensities of HMGB1, SOX9, and YAP1 were elevated in CCA tissues than the adjacent normal tissues. Individual scoring of subcellular localization revealed that the expression levels of HMGB1 (nucleus) and YAP1 (nucleus and cytoplasm) were significantly different from the pathologic M stage. Moreover, the translocation pattern was categorized using “site-index”, and the results demonstrated that the overexpression of HMGB1 and SOX9 was mostly observed in both the nucleus and cytoplasm, whereas YAP1 was predominantly expressed in the cytoplasm of tumor cells. Interestingly, the site index of HMGB1 was moderately correlated with the tumor stage (r = 0.441, p = 0.031). These findings imply that the overexpression of subcellular HMGB1 could be associated with the metastatic status of patients with CS-CCA, which was shown to be effective for CS-CCA prognosis.

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Expression of SOX9 Is Related to Prognosis in Patients with Oesophageal Squamous Cell Carcinoma

Abstract: SOX9 expression is related to prognosis in patients with oesophageal squamous cell carcinoma, although it is not an independent prognostic factor.

Cited by 8 publications

References 13 publications

<p>microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway</p>

<p>microRNA-605 directly targets SOX9 to alleviate the aggressive phenotypes of glioblastoma multiforme cell lines by deactivating the PI3K/Akt pathway</p>

Constructing and identifying an eighteen-gene Tumor Microenvironment Prognostic Model for Non-Small Cell Lung Cancer

Subcellular localization of HMGB1 in human cholangiocarcinoma: correlation with tumor stage

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