SOX9: Advances in Gynecological Malignancies

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Dec 9

PMID 34881182

Citations 4

Authors

Huan Chen

Yujie He

Xiangping Wen

Shihong Shao

Yujie Liu

Jinjin Wang

Affiliations

Soon will be listed here.

Abstract

Transcription factors of the SOX family were first discovered in mammals in 1990. The sex-determining region Y box 9 belongs to the SOX transcription factor family. It plays an important role in inducing tissue and cell morphogenesis, survival, and many developmental processes. Furthermore, it has been shown to be an oncogene in many tumors. Gynecological malignancies are tumors that occur in the female reproductive system and seriously threaten the lives of patients. Common gynecological malignancies include ovarian cancer, cervical cancer, and endometrial cancer. So far, the molecular mechanisms related to the incidence and development of gynecological malignancies remain unclear. This makes it particularly important to discover their common causative molecule and thus provide an effective therapeutic target. In recent years, studies have found that multiple mechanisms are involved in regulating the expression of the sex-determining region Y box 9, leading to the occurrence and development of gynecological malignancies. In this review, we discuss the prognostic value of expression and the potential of targeting for gynecological malignancy treatment. We also discuss progress regarding the role of in gynecological malignancy pathogenesis through its mediation of important mechanisms, including tumor initiation and proliferation, apoptosis, migration, invasion, chemoresistance, and stem cell maintenance.

Citing Articles

Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 3 Expression and Its Correlation with Prognosis and Growth of Serous Ovarian Cancer: Correlation of DYRK3 with Ovarian Cancer Survival.

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PMID: 38529261 PMC: 10963101. DOI: 10.1155/2024/6683202.

Role of SOX9 and Hif-1α expression in placentas of patients with HELLP.

Akalin S, Ocal E, Deveci E Acta Cir Bras. 2023; 38:e388023.

PMID: 37878989 PMC: 10592703. DOI: 10.1590/acb388023.

New insights into KLFs and SOXs in cancer pathogenesis, stemness, and therapy.

Zeng L, Zhu Y, Moreno C, Wan Y Semin Cancer Biol. 2023; 90:29-44.

PMID: 36806560 PMC: 10023514. DOI: 10.1016/j.semcancer.2023.02.003.

Prognostic value of in cervical cancer: Bioinformatics and experimental approaches.

Chen H, Chen X, Zeng F, Fu A, Huang M Front Genet. 2022; 13:939328.

PMID: 36003340 PMC: 9394184. DOI: 10.3389/fgene.2022.939328.

References

Masuda T, Low S, Akiyama M, Hirata M, Ueda Y, Matsuda K . GWAS of five gynecologic diseases and cross-trait analysis in Japanese. Eur J Hum Genet. 2019; 28(1):95-107. PMC: 6906293. DOI: 10.1038/s41431-019-0495-1. View

Sudbeck P, Scherer G . Two independent nuclear localization signals are present in the DNA-binding high-mobility group domains of SRY and SOX9. J Biol Chem. 1997; 272(44):27848-52. DOI: 10.1074/jbc.272.44.27848. View

Davis S, Propp S, Freier S, Jones L, Serra M, Kinberger G . Potent inhibition of microRNA in vivo without degradation. Nucleic Acids Res. 2008; 37(1):70-7. PMC: 2615630. DOI: 10.1093/nar/gkn904. View

Yamashita S, Kataoka K, Yamamoto H, Kato T, Hara S, Yamaguchi K . Comparative analysis demonstrates cell type-specific conservation of SOX9 targets between mouse and chicken. Sci Rep. 2019; 9(1):12560. PMC: 6715657. DOI: 10.1038/s41598-019-48979-4. View

Papanastasopoulos P, Repanti M, Damaskou V, Bravou V, Papadaki H . Investigating differentiation mechanisms of the constituent cells of sex cord-stromal tumours of the ovary. Virchows Arch. 2008; 453(5):465-71. DOI: 10.1007/s00428-008-0677-7. View

Kato N, Fukase M, Motoyama T . Expression of a transcription factor, SOX9, in Sertoli-stromal cell tumors of the ovary. Int J Gynecol Pathol. 2004; 23(2):180-1. DOI: 10.1097/00004347-200404000-00014. View

An Y, Wang Q, Sun F, Zhang G, Wang F, Zhang L . OSucs: An Online Prognostic Biomarker Analysis Tool for Uterine Carcinosarcoma. Genes (Basel). 2020; 11(9). PMC: 7563768. DOI: 10.3390/genes11091040. View

Shi G, Sohn K, Li Z, Choi D, Park Y, Kim J . Expression and functional role of Sox9 in human epidermal keratinocytes. PLoS One. 2013; 8(1):e54355. PMC: 3548846. DOI: 10.1371/journal.pone.0054355. View

Li J, Peng W, Yang P, Chen R, Gu Q, Qian W . MicroRNA-1224-5p Inhibits Metastasis and Epithelial-Mesenchymal Transition in Colorectal Cancer by Targeting SP1-Mediated NF-κB Signaling Pathways. Front Oncol. 2020; 10:294. PMC: 7083241. DOI: 10.3389/fonc.2020.00294. View

10.

Richtig G, Aigelsreiter A, Schwarzenbacher D, Ress A, Adiprasito J, Stiegelbauer V . SOX9 is a proliferation and stem cell factor in hepatocellular carcinoma and possess widespread prognostic significance in different cancer types. PLoS One. 2017; 12(11):e0187814. PMC: 5679634. DOI: 10.1371/journal.pone.0187814. View

11.

Wang H, Leav I, Ibaragi S, Wegner M, Hu G, Lu M . SOX9 is expressed in human fetal prostate epithelium and enhances prostate cancer invasion. Cancer Res. 2008; 68(6):1625-30. DOI: 10.1158/0008-5472.CAN-07-5915. View

12.

Chang X, Li D, Liu C, Zhang Z, Wang T . Pentraxin 3 is a diagnostic and prognostic marker for ovarian epithelial cancer patients based on comprehensive bioinformatics and experiments. Cancer Cell Int. 2021; 21(1):193. PMC: 8097951. DOI: 10.1186/s12935-021-01854-7. View

13.

Feng C, Ma F, Hu C, Ma J, Wang J, Zhang Y . SOX9/miR-130a/CTR1 axis modulates DDP-resistance of cervical cancer cell. Cell Cycle. 2017; 17(4):448-458. PMC: 5927693. DOI: 10.1080/15384101.2017.1395533. View

14.

Zhao J, Li H, Yuan M . EGR1 promotes stemness and predicts a poor outcome of uterine cervical cancer by inducing SOX9 expression. Genes Genomics. 2021; 43(5):459-470. DOI: 10.1007/s13258-021-01064-5. View

15.

Li Y, Liu J, Piao J, Ou J, Zhu X . Circ_0109046 promotes the malignancy of endometrial carcinoma cells through the microRNA-105/SOX9/Wnt/β-catenin axis. IUBMB Life. 2020; 73(1):159-176. DOI: 10.1002/iub.2415. View

16.

Zhu W, Xiao X, Chen J . Silencing of the long noncoding RNA LINC01132 alleviates the oncogenicity of epithelial ovarian cancer by regulating the microRNA‑431‑5p/SOX9 axis. Int J Mol Med. 2021; 48(2). PMC: 8219520. DOI: 10.3892/ijmm.2021.4984. View

17.

Hattori T, Kishino T, Stephen S, Eberspaecher H, Maki S, Takigawa M . E6-AP/UBE3A protein acts as a ubiquitin ligase toward SOX9 protein. J Biol Chem. 2013; 288(49):35138-48. PMC: 3853265. DOI: 10.1074/jbc.M113.486795. View

18.

Kao C, Idrees M, Young R, Ulbright T . "Dissecting Gonadoblastoma" of Scully: A Morphologic Variant That Often Mimics Germinoma. Am J Surg Pathol. 2016; 40(10):1417-23. DOI: 10.1097/PAS.0000000000000704. View

19.

Chen Q, Tong M, Guo F, Lau S, Zhao M . Parity Correlates with the Timing of Developing Endometrial Cancer, But Not Subtype of Endometrial Cancer. J Cancer. 2015; 6(11):1087-92. PMC: 4615343. DOI: 10.7150/jca.12736. View

20.

Saegusa M, Hashimura M, Suzuki E, Yoshida T, Kuwata T . Transcriptional up-regulation of Sox9 by NF-κB in endometrial carcinoma cells, modulating cell proliferation through alteration in the p14(ARF)/p53/p21(WAF1) pathway. Am J Pathol. 2012; 181(2):684-92. DOI: 10.1016/j.ajpath.2012.05.008. View