Expression and Clinical Significance of SOX9 in Renal Cell Carcinoma, Bladder Cancer and Penile Cancer

Wan, Yuqing; Xi, Mian; He, Hui‐Chan; Song, Wan; Hua, Wei; Zen, Zhao-Chang; Liu, Yuanling; Zhou, Yanmin; Mo, Rujun; Zhuo, Yangjia; Luo, Hongwei; Jiang, Funeng; Zhong, Weide

doi:10.1159/000455145

Cited by 21 publications

(21 citation statements)

References 24 publications

(25 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, we evaluated the expressions of some SOX members including SOX4, SOX9 and another two SOXD members (SOX5 and SOX13) in ccRCC. In consistent with previous studies, 28,29 the mRNA levels of SOX4 and SOX9 were significantly upregulated in ccRCC tissues compared with adjacent nontumorous tissues (Figure S1A,B). However, there was no significant difference in the expressions of SOX5 and SOX13 between ccRCC and nontumorous tissues from TCGA dataset (Figure S1C,D).…”

Section: Resultssupporting

confidence: 92%

“…Because SOX6 has been shown to co‐stimulate SOX9 target genes (Col2a1 and Agc1) in chondrocytes 39 and SOX9 is involved in ccRCC growth, 29,32 it is possible that the role of SOX6 is ccRCC is in part due to regulation of SOX9 target genes. To test this hypothesis, we investigated the impact of SOX6 on the expressions of SOX4 and SOX9 in ccRCC cell lines.…”

Section: Resultsmentioning

confidence: 99%

“…As for SOX9, Li et al 32 found that SOX9 was highly expressed in ccRCC and its expression was involved in Tyrosine kinase inhibitors drug resistance through activation of Raf/MEK/ERK pathway. In addition, another study evaluating SOX9 protein expression in ccRCC tissue microarrays (TMA) also found that SOX9 expression was significantly elevated in ccRCC and its expression was positively correlated with advanced grade and stage and negatively correlated with survival 29 . These findings suggest that SOX9 might play an important role in ccRCC tumor progression.…”

Section: Introductionmentioning

confidence: 92%

“…So far, several studies have been conducted to explore the roles of some SOX members including SOX4 and SOX9 in ccRCC 28,29 . Wu et al 30 and Tong et al 31 found that miR‐204 and miR‐338‐3p could inhibit cell proliferation, migration and invasion in ccRCC cell lines by directly targeting SOX4, respectively.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

Chen

Xie

et al. 2020

Molecular Carcinogenesis

View full text Add to dashboard Cite

Sex‐determining region Y box (SOXs) are expressed in various cells and control cell fate and differentiation in a multitude of physiologic processes. SOX6, a main representative of SOXs, is involved in the regulation of carcinogenesis in various human malignancies. However, the role of SOX6 in clear cell renal cell carcinoma (ccRCC) remains unclear. In this study, SOX6 expression in ccRCC and its clinical significance were investigated. In vitro and in vivo assays were used to explore the tumor‐related function and the underlying molecular mechanism of SOX6 in ccRCC. We confirmed that SOX6 was frequently downregulated in ccRCC tissues and cell lines. Besides, downregulation of SOX6 was significantly associated with larger tumor sizes, advanced tumor stage, higher Fuhrman grades, and its expression could act as an independent prognostic factor for ccRCC (hazards ratio = 0.590, P = .026). Gain/loss‐of‐function experiments demonstrated that SOX6 could remarkably inhibit tumor cell growth and foci formation in vitro and xenograft tumorigenesis in vivo, respectively. Mechanistically, SOX6 could influence cell cycle by regulating the G1/the S phase transition and had an inhibitory effect on Wnt/β‐catenin signaling as well as its target genes, c‐Myc and cyclin D1. Interesting, the tumor‐suppressive function of SOX6 was proved to be dependent on its specific high‐mobility‐group (HMG) domain. In general, our findings indicated that SOX6 was a novel tumor suppressor and prognostic biomarker in ccRCC. SOX6 could inhibit tumor growth by negatively regulating the Wnt/β‐catenin signaling pathway in an HMG domain‐dependent manner in ccRCC, which might provide a novel therapeutic approach for ccRCC.

show abstract

Section: Resultssupporting

confidence: 92%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

Chen

Xie

et al. 2020

Molecular Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…Besides, overexpression of SOX9 is related to clinicopathological characteristics, such as the advanced pathological grade and clinical stage. Also, SOX9 is an independent predictor factor for the survival of RCC patients in the TCGA dataset [27].…”

Section: Sox9 Is Overexpressed In Crc Tumors and Cell Linesmentioning

confidence: 98%

Cell Survival Is Regulated via SOX9/BCL2L1 Axis in HCT-116 Colorectal Cancer Cell Line

Lizárraga-Verdugo

Ruiz‐García

López-Camarillo

et al. 2020

Journal of Oncology

View full text Add to dashboard Cite

Colorectal cancer (CRC) is one of the most frequent types of malignancies and one of the major causes of cancer-related death worldwide. Sex-determining region Y (SRY)-box 9 protein (SOX9) is a member of the SOX family of transcription factors which are involved in the regulation of differentiation and development. Recently, several reports suggest an important role of SOX9 in tumorigenesis since its overexpression correlates with tumor progression and poor outcome in several types of cancer; however, its role in CRC is not clear until now. Therefore, in this work, we searched for novel SOX9-regulated genes involved in cell survival of CRC. We silenced SOX9 in the poorly differentiated HCT-116 cell line, using a specific siRNA, to identify differential expressed genes by DNA microarrays and analyzed the role or candidate genes in apoptosis and autophagy. Transcriptome analysis showed that diverse cellular pathways, associated with CRC carcinogenesis such as Wnt/β-catenin, MAPK, TGF-β, and mTOR, were modulated after SOX9 silencing. Interestingly, we found that SOX9 silencing promotes downregulation of BCL2L1 and overexpression of CASP3, proteins related to apoptosis, which was further confirmed in SW-480, a moderated-differentiated cell line, but not in HT-29, well-differentiated cell line. Moreover, inhibition of BCL2L1 by ABT-737 (BH3 mimetic) in SOX9-silenced HCT-116 cells resulted in an increased apoptosis percentage. However, downregulation of BCL2L1 was not enough to induce autophagy. This is the first report, suggesting that cell survival in poorly and moderated-differentiated CRC cells lines is regulated by SOX9/BCL2L1 axis, but not in well-differentiated cell lines.

show abstract

Expression profiles of Sox transcription factors within the postnatal rodent testes

2018

View full text Add to dashboard Cite

SRY-related box (Sox) transcription factors are conserved among vertebrate species. These proteins regulate multiple processes including sex determination and testis differentiation of the male embryo. Members of the Sox family have been identified in pre- and postnatal testis and are known to play an important role in sex determination (Sry, Sox9), male gonadal development, and fertility (Sox4, Sox8, Sox30). However, their expression profiles per cell types remain elusive. The objectives of this research were to characterize the expression profiles of Sox family members within adult testes using publically available datasets and to determine whether these findings are consistent with literature as well as immunofluorescence and in situ hybridization results. We have found that Sox4, Sox8, Sox9, and Sox12 are highly expressed in Sertoli cells, whereas Sox5, Sox6, and Sox30 were typically expressed in spermatocytes and spermatids. Spermatogonia were characterized by the expressions of Sox3, Sox4, Sox12, Sox13, and Sox18. Hence, these results suggest that Sox transcription factors may play different roles according to cell types of the adult mammalian testis.

show abstract

Expression and Clinical Significance of SOX9 in Renal Cell Carcinoma, Bladder Cancer and Penile Cancer

Cited by 21 publications

References 24 publications

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

SOX6 represses tumor growth of clear cell renal cell carcinoma by HMG domain‐dependent regulation of Wnt/β‐catenin signaling

Cell Survival Is Regulated via SOX9/BCL2L1 Axis in HCT-116 Colorectal Cancer Cell Line

Expression profiles of Sox transcription factors within the postnatal rodent testes

Contact Info

Product

Resources

About