Upregulated SOX9 expression indicates worse prognosis in solid tumors: a systematic review and meta-analysis

Ruan, Haihua; Hu, Shuangyan; Zhang, Hongyu; Du, Gang; Li, Xiaoting; Li, Xiaobo; Li, Xichuan

doi:10.18632/oncotarget.22635

Cited by 21 publications

(15 citation statements)

References 51 publications

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“…10 A recent review comparing the overall survival of patients of solid tumours with the overexpression of SOX9 revealed an obvious tumour growth promotion by SOX9. 15 These studies are consistent with our finding whereby SOX9 were upregulated in both grades of glioma. However, SOX9 was found in all grades of glioma with slightly lower expression in pilocytic astrocytomas during protein analysis.…”

Section: Discussionsupporting

confidence: 92%

“…The function of SOX9 in maintaining progenitor cells during proliferation and differentiation in embryogenesis and adult, if disrupted could possibly lead to cancer. 14,15 In line with this, SOX9 shows overexpression in many types of cancer and the expression correlated with malignancy and progression of cancer. 7,15 SOX9 was shown to play a role as oncogene via overexpression in multiple types of cancer such as colorectal, glioma, and pancreatic cancers.…”

Section: Introductionmentioning

confidence: 56%

“…14,15 In line with this, SOX9 shows overexpression in many types of cancer and the expression correlated with malignancy and progression of cancer. 7,15 SOX9 was shown to play a role as oncogene via overexpression in multiple types of cancer such as colorectal, glioma, and pancreatic cancers. 7,10,16 SOX factors lead to tumourigenesis by regulating β-catenin/TCF activity and the oncogenic Wnt-target genes expression such as Cyclin-D1 and c-Myc.…”

Section: Introductionmentioning

confidence: 56%

“…25 SOX9 is believed to play an important roles in glioma progression and development due to its propensity to elevate the expression according to WHO grading progression. 10,15 In the light of the recent micro-RNAs involvement in cancer research, several oncogenes miRNAs have been identified to be overexpressed in glioma including miR-21, miR-328, miR-145 and miR-105, while several of the miRNAs act as tumour suppressor and being downregulated for instance, miR-137 and miR-6500-3p. There was evidence that SOX9 acts as a direct target of miR-105 and miR-145 in glioma.…”

Section: Discussionmentioning

confidence: 99%

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Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

Nb¹,

Wr²,

Mn³

et al. 2020

imjm

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Introduction: SOX9, a members of SOX family, plays a significant roles in developmental processes during embryogenesis, including brain tissue. Few studies have shown that SOX9 has been involved in tumourigenesis of several types of cancer including brain tumour. However, such studies are still lacking in the Malaysian population. The aim of this study was to determine SOX9 expression level in several types of brain tumours in East Coast Malaysia. Materials and Methods: Five formalin-fixed pariffin-embedded brain tumour samples of Malay descendants were sectioned by using microtome. RNA extraction was performed with slight modification by adding Trizol during tissue lysis. The RNA was converted to cDNA using reverse transcription technique before SOX9 expression was detected using RT q-PCR assay in brain tumours normalized to non-neoplastic brain tissues. Results: Overall results displayed that SOX9 gene in all samples were up-regulated. SOX9 overexpression was found in both high and low grade glioma (anaplastic and pilocytic astrocytoma respectively). This is consistence with both low grade (benign) and atypical meningioma. Secondary brain tumour also showed up-regulation when compared to normal brain tissue. Conclusion: Up-regulation in SOX9 expression in selected brain tumours in Malay patients revealed its significant roles in brain tumourigenesis. Functional studies should be carried out to observe the SOX9 functions and mechanism whether they should reflect their diverse roles in Malaysia population.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 56%

Section: Introductionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

Nb¹,

Wr²,

Mn³

et al. 2020

imjm

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“…In clinical samples, SOX9 expression is elevated in glioblastoma, pancreatic ductal adenocarcinoma, gastric cancer, colon, skin or breast cancer samples respect to adjacent normal tissue [28][29][30] . Furthermore, high levels of SOX9 have been associated with tumor grade, dismal prognosis and poor patient survival in patients of those types of cancer 28,31,32 . Thus, SOX9 expression and function are altered in diverse human cancers, acting as an oncogene in a wide range of them, mainly through the regulation of CSCs activity, and as a tumor suppressor in specific situations 26 .…”

mentioning

confidence: 99%

SOX9 promotes tumor progression through the axis BMI1-p21CIP

Aldaz

Otaegi-Ugartemendia

Saenz-Antoñanzas

et al. 2020

Sci Rep

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The developmental regulator SOX9 is linked to cancer progression mainly as a result of its role in the regulation of cancer stem cells (CSCs). However, its activity in the differentiated cells that constitute the heterogeneous tumor bulk has not been extensively studied. In this work, we addressed this aspect in gastric cancer, glioblastoma and pancreatic adenocarcinoma. SOX9 silencing studies revealed that SOX9 is required for cancer cell survival, proliferation and evasion of senescence in vitro and tumor growth in vivo. Gain of-SOX9 function showed that high levels of SOX9 promote tumor cell proliferation in vitro and in vivo. Mechanistically, the modulation of SOX9 changed the expression of the transcriptional repressor BMI1 in the same direction in the three types of cancer, and the expression of the tumor suppressor p21 cip in the opposite direction. In agreement with this, SOX9 expression positively correlated with BMI1 levels and inversely with p21 cip in clinical samples of the different cancers. Moreover, BMI1 re-establishment in SOX9-silenced tumor cells restored cell viability and proliferation as well as decreased p21 cip in vitro and tumor growth in vivo. These results indicate that BMI1 is a critical effector of the pro-tumoral activity of SOX9 in tumor bulk cells through the repression of p21 cip. Our results highlight the relevance of the SOX9-BMI1-p21 cip axis in tumor progression, shedding novel opportunities for therapeutic development. Some types of cancer exhibit a dismal prognosis, mainly due to its late diagnosis, its aggressive progression and the resistance to the available chemotherapy, in which inter and intra-tumoral heterogeneity play a major role 1,2. One of these types of cancer is pancreatic ductal adenocarcinoma (PDAC), with a 5-year survival rate of less than 6% 3 and very similar rates of incidence and mortality (458,918 new diagnoses and 432,242 deaths worldwide in 2018) 4. Glioblastoma (GBM), the most malignant primary brain tumor, also represents a challenge in oncology despite having a low incidence (less than 5 cases per 100,000 people), as exhibits a 5-year survival rate of 5.6% 5 and a median survival of 14.6 months 6. For its part, gastric cancer (GC) is the third leading cause of cancer deaths worldwide, with an estimated 783,000 deaths in 2018 4. SOX9 [SRY (Sex determining region Y)-box 9] is a member of the SOX family of transcription factors, which are developmental regulators characterized by a conserved high mobility group (HMG) DNA-binding domain 7. SOX9 regulates stem cell maintenance and instruction of cell fate, and exerts relevant roles during development, such as sex determination, neural crest development, chondrogenesis or pancreas development 8-10. During embryogenesis, SOX9 is expressed and regulates progenitor proliferation and differentiation, being required for maintaining tissue identity in different contexts, but mainly in the brain and gastrointestinal system 10-12. Likewise, in the adulthood, SOX9 also plays a relevant role in the maintenance of t...

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A Spheroid Model of Early and Late‐Stage Osteosarcoma Mimicking the Divergent Relationship between Tumor Elimination and Bone Regeneration

Freeman

Burdis

Mahon

et al. 2021

Adv Healthcare Materials

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Osteosarcoma is the most diagnosed bone tumor in children. The use of tissue engineering strategies after malignant tumor resection remains a subject of scientific controversy. As a result, there is limited research that focuses on bone regeneration postresection, which is further compromised following chemotherapy. This study aims to develop the first co-culture spheroid model for osteosarcoma, to understand the divergent relationship between tumor elimination and bone regeneration. By manipulating the ratio of stromal to osteosarcoma cells the modelled cancer state (early/late) is modified, as is evident by the increased tumor growth rates and an upregulation of a panel of well-established osteosarcoma prognostic genes. Validation of the authors' model is conducted by analyzing its ability to mimic the cytotoxic effects of the FDA-approved chemotherapeutic Doxorubicin. Next, the model is used to investigate what effect osteogenic supplements have, if any, on tumor growth. When their model is treated with osteogenic supplements, there is a stimulatory effect on the surrounding stromal cells. However, when treated with chemotherapeutics this stimulatory effect is significantly diminished. Together, the results of this study present a novel multicellular model of osteosarcoma and provide a unique platform for screening potential therapeutic options for osteosarcoma before conducting in vivo experiments.

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Upregulated SOX9 expression indicates worse prognosis in solid tumors: a systematic review and meta-analysis

Cited by 21 publications

References 51 publications

Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

Determination of SOX9 Gene Expression In Brain Tumours Among East Coast Malaysia Population

SOX9 promotes tumor progression through the axis BMI1-p21CIP

A Spheroid Model of Early and Late‐Stage Osteosarcoma Mimicking the Divergent Relationship between Tumor Elimination and Bone Regeneration

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