SOX4: Epigenetic Regulation and Role in Tumorigenesis.

Sex-determining region Y-related (SRY) high-mobility group box 4 (SOX4) is a member of the group C subfamily of SOX transcription factors and promotes tumorigenesis by endowing cancer cells with survival, migratory, and invasive capacities. Emerging evidence has highlighted an unequivocal role for this transcription factor in mediating various signaling pathways involved in tumorigenesis, epithelial-to-mesenchymal transition (EMT), and tumor progression. During the last decade, numerous studies have highlighted the epigenetic interplay between SOX4-targeting microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and SOX4 and the subsequent modulation of tumorigenesis, invasion and metastasis. In this review, we summarize the current state of knowledge about the role of SOX4 in cancer development and progression, the epigenetic regulation of SOX4, and the potential utilization of SOX4 as a diagnostic and prognostic biomarker and its depletion as a therapeutic target.

[1]  Lin Wang,et al.  Association of SOX4 regulated by tumor suppressor miR-30a with poor prognosis in low-grade chondrosarcoma , 2015, Tumor Biology.

[2]  B. Han,et al.  ERG–SOX4 interaction promotes epithelial–mesenchymal transition in prostate cancer cells , 2014, The Prostate.

[3]  M. Kassem,et al.  Circulating microRNAs in breast cancer: novel diagnostic and prognostic biomarkers , 2017, Cell Death & Disease.

[4]  Peng Zhang,et al.  MiR-129-5p Inhibits Proliferation and Invasion of Chondrosarcoma Cells by Regulating SOX4/Wnt/β-Catenin Signaling Pathway , 2017, Cellular Physiology and Biochemistry.

[5]  L. Zentilin,et al.  Functional screening identifies miRNAs inducing cardiac regeneration , 2012, Nature.

[6]  Raghu Kalluri,et al.  The basics of epithelial-mesenchymal transition. , 2009, The Journal of clinical investigation.

[7]  Einat Sitbon,et al.  hsa-miR-191 is a candidate oncogene target for hepatocellular carcinoma therapy. , 2010, Cancer research.

[8]  K. Thirugnanasambantham,et al.  Novel Aryl Hydrocarbon Receptor Agonist Suppresses Migration and Invasion of Breast Cancer Cells , 2016, PloS one.

[9]  Xiaoling Lin,et al.  Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 in gastric cancer. , 2010, Biochemical and biophysical research communications.

[10]  A. Zorn,et al.  Interactions between SOX factors and Wnt/β‐catenin signaling in development and disease , 2009, Developmental dynamics : an official publication of the American Association of Anatomists.

[11]  H. Allgayer,et al.  MicroRNA-21 (miR-21) post-transcriptionally downregulates tumor suppressor Pdcd4 and stimulates invasion, intravasation and metastasis in colorectal cancer , 2008, Oncogene.

[12]  Baoli Hu,et al.  LncRNA CCAT1/miR-130a-3p axis increases cisplatin resistance in non-small-cell lung cancer cell line by targeting SOX4 , 2017, Cancer biology & therapy.

[13]  D. Birnbaum,et al.  MicroRNA93 Regulates Proliferation and Differentiation of Normal and Malignant Breast Stem Cells , 2012, PLoS genetics.

[14]  Hamza Hanieh,et al.  Aryl hydrocarbon receptor-microRNA-212/132 axis in human breast cancer suppresses metastasis by targeting SOX4 , 2015, Molecular Cancer.

[15]  P. Brown,et al.  Large-scale meta-analysis of cancer microarray data identifies common transcriptional profiles of neoplastic transformation and progression. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  P. Jacquemin,et al.  Transcription factors SOX4 and SOX9 cooperatively control development of bile ducts. , 2015, Developmental biology.

[17]  Chao Li,et al.  Celecoxib induces epithelial-mesenchymal transition in epithelial ovarian cancer cells via regulating ZEB1 expression , 2015, Archives of Gynecology and Obstetrics.

[18]  W. Gerald,et al.  Endogenous human microRNAs that suppress breast cancer metastasis , 2008, Nature.

[19]  X. Li,et al.  MiR-129-5p is downregulated in breast cancer cells partly due to promoter H3K27m3 modification and regulates epithelial-mesenchymal transition and multi-drug resistance. , 2016, European Review for Medical and Pharmacological Sciences.

[20]  Young Yang,et al.  Suppression of NF-kappaB activity by NDRG2 expression attenuates the invasive potential of highly malignant tumor cells. , 2009, Carcinogenesis.

[21]  Juan Sun,et al.  MiR-211 inhibits cell proliferation and invasion of gastric cancer by down-regulating SOX4. , 2015, International journal of clinical and experimental pathology.

[22]  Xiangmei Chen,et al.  Methylation‐mediated repression of microRNA 129‐2 enhances oncogenic SOX4 expression in HCC , 2013, Liver international : official journal of the International Association for the Study of the Liver.

[23]  Qingsan Zhu,et al.  MicroRNA-132 inhibits cell growth and metastasis in osteosarcoma cell lines possibly by targeting Sox4 , 2015, International journal of oncology.

[24]  K. Helin,et al.  Molecular Mechanisms Directing PRC2 Recruitment and H3K27 Methylation. , 2019, Molecular cell.

[25]  G. Yao,et al.  MicroRNA-320 inhibits cell proliferation and invasion in breast cancer cells by targeting SOX4 , 2017, Oncology letters.

[26]  Zhen Lu,et al.  Histological and Pathological Assessment of miR-204 and SOX4 Levels in Gastric Cancer Patients , 2017, BioMed research international.

[27]  V. Lefebvre,et al.  SOX4 enables oncogenic survival signals in acute lymphoblastic leukemia. , 2013, Blood.

[28]  C. Heldin,et al.  Regulation of EMT by TGFβ in cancer , 2012, FEBS letters.

[29]  M. Martinka,et al.  Prognostic significance of Sox4 expression in human cutaneous melanoma and its role in cell migration and invasion. , 2010, The American journal of pathology.

[30]  Yan Shen,et al.  An androgen receptor negatively induced long non-coding RNA ARNILA binding to miR-204 promotes the invasion and metastasis of triple-negative breast cancer , 2018, Cell Death & Differentiation.

[31]  J. Zou,et al.  MicroRNA-140 Inhibits Cell Proliferation in Gastric Cancer Cell Line HGC-27 by Suppressing SOX4 , 2016, Medical science monitor : international medical journal of experimental and clinical research.

[32]  K. Chao,et al.  MicroRNA‐138 suppresses ovarian cancer cell invasion and metastasis by targeting SOX4 and HIF‐1α , 2013, International journal of cancer.

[33]  Chi-Hung Huang,et al.  Bmi1 is essential in Twist1-induced epithelial–mesenchymal transition , 2010, Nature Cell Biology.

[34]  K. Miyazono,et al.  Glioma-initiating Cells Retain Their Tumorigenicity through Integration of the Sox Axis and Oct4 Protein* , 2011, The Journal of Biological Chemistry.

[35]  Piotr J. Balwierz,et al.  Sox4 is a master regulator of epithelial-mesenchymal transition by controlling Ezh2 expression and epigenetic reprogramming. , 2013, Cancer cell.

[36]  K. Grasser,et al.  The HMG-box: a versatile protein domain occurring in a wide variety of DNA-binding proteins , 2007, Cellular and Molecular Life Sciences.

[37]  F. Slack,et al.  RAS Is Regulated by the let-7 MicroRNA Family , 2005, Cell.

[38]  D. Hanahan,et al.  Hallmarks of Cancer: The Next Generation , 2011, Cell.

[39]  W. Rao,et al.  MicroRNA-19a-3p suppresses invasion and metastasis of prostate cancer via inhibiting SOX4. , 2018, European review for medical and pharmacological sciences.

[40]  James B. Shealy,et al.  miR-1269 Promotes Metastasis and Forms a Positive Feedback Loop with TGF-β , 2015, Nature Communications.

[41]  Xin-Rong Zhan,et al.  MicroRNA-204 inhibits cell proliferation in T-cell acute lymphoblastic leukemia by down-regulating SOX4. , 2015, International journal of clinical and experimental pathology.

[42]  Ziwei Wang,et al.  SOX4 contributes to TGF-β-induced epithelial–mesenchymal transition and stem cell characteristics of gastric cancer cells , 2017, Genes & diseases.

[43]  Cun-Yu Wang,et al.  STAT3-mediated upregulation of lncRNA HOXD-AS1 as a ceRNA facilitates liver cancer metastasis by regulating SOX4 , 2017, Molecular Cancer.

[44]  Raghu Kalluri,et al.  EMT: when epithelial cells decide to become mesenchymal-like cells. , 2009, The Journal of clinical investigation.

[45]  A. Bradley,et al.  Identification of mammalian microRNA host genes and transcription units. , 2004, Genome research.

[46]  X. Tian,et al.  UCA1 promotes cell proliferation and invasion and inhibits apoptosis through regulation of the miR129–SOX4 pathway in renal cell carcinoma , 2018, OncoTargets and therapy.

[47]  C. Moskaluk,et al.  Knockdown of Sox4 expression by RNAi induces apoptosis in ACC3 cells , 2006, Oncogene.

[48]  Qinghua Zhou,et al.  MicroRNA-338-3p suppresses metastasis of lung cancer cells by targeting the EMT regulator Sox4. , 2016, American journal of cancer research.

[49]  Fei-Fei Liu,et al.  MicroRNA-320 suppresses colorectal cancer by targeting SOX4, FOXM1, and FOXQ1 , 2016, Oncotarget.

[50]  Michael K. Wendt,et al.  Deconstructing the mechanisms and consequences of TGF-β-induced EMT during cancer progression , 2011, Cell and Tissue Research.

[51]  P. Coffer,et al.  SOX4: Joining the Master Regulators of Epithelial-to-Mesenchymal Transition? , 2017, Trends in cancer.

[52]  Guoxin Zhang,et al.  Decreased miR-204 in H. pylori-Associated Gastric Cancer Promotes Cancer Cell Proliferation and Invasion by Targeting SOX4 , 2014, PloS one.

[53]  N. Lu,et al.  A new role for the PI3K/Akt signaling pathway in the epithelial-mesenchymal transition , 2015, Cell adhesion & migration.

[54]  Y. Hseu,et al.  Clinical and Prognostic Association of Transcription Factor SOX4 in Gastric Cancer , 2012, PloS one.

[55]  A. Krogh,et al.  Programmed Cell Death 4 (PDCD4) Is an Important Functional Target of the MicroRNA miR-21 in Breast Cancer Cells* , 2008, Journal of Biological Chemistry.

[56]  Ju-Seog Lee,et al.  Integrated genetic approaches identify the molecular mechanisms of Sox4 in early B-cell development: intricate roles for RAG1/2 and CK1ε. , 2014, Blood.

[57]  C. Croce,et al.  MiRNAs and cancer. , 2009, The American journal of pathology.

[58]  Kai-Yuan Lin,et al.  Clinical and Prognostic Implications of Transcription Factor SOX4 in Patients with Colon Cancer , 2013, PloS one.

[59]  Sang‐Gun Ahn,et al.  Sox4 stimulates ß-catenin activity through induction of CK2. , 2011, Oncology reports.

[60]  Liangchen Niu,et al.  miR-138 inhibits gastric cancer growth by suppressing SOX4. , 2017, Oncology reports.

[61]  W. G. Wiles,et al.  SOX4 Is Essential for Prostate Tumorigenesis Initiated by PTEN Ablation. , 2016, Cancer research.

[62]  A. Hui,et al.  MiR-218 suppresses nasopharyngeal cancer progression through downregulation of survivin and the SLIT2-ROBO1 pathway. , 2011, Cancer research.

[63]  Haihong Jin,et al.  MiR-212/132 is epigenetically downregulated by SOX4/EZH2-H3K27me3 feedback loop in ovarian cancer cells , 2016, Tumor Biology.

[64]  Daixing Zhou,et al.  Increased expression of SOX4 is a biomarker for malignant status and poor prognosis in patients with non-small cell lung cancer , 2015, Molecular and Cellular Biochemistry.

[65]  S. Safe,et al.  Aryl Hydrocarbon Receptor Agonists Induce MicroRNA-335 Expression and Inhibit Lung Metastasis of Estrogen Receptor Negative Breast Cancer Cells , 2011, Molecular Cancer Therapeutics.

[66]  You-guang Huang,et al.  Down‐regulated SOX4 Expression Suppresses Cell Proliferation, Metastasis and Induces Apoptosis in Xuanwei Female Lung Cancer Patients , 2015, Journal of cellular biochemistry.

[67]  Hui-Juan Xie,et al.  FOXC2 promotes epithelial–mesenchymal transition and cisplatin resistance of non-small cell lung cancer cells , 2018, Cancer Chemotherapy and Pharmacology.

[68]  Hong Hao,et al.  miR-129-2 suppresses proliferation and migration of esophageal carcinoma cells through downregulation of SOX4 expression. , 2013, International journal of molecular medicine.

[69]  Colleen D. McCabe,et al.  Genome-wide promoter analysis of the SOX4 transcriptional network in prostate cancer cells. , 2009, Cancer research.

[70]  Y. Shen,et al.  Long noncoding RNA CASC2 inhibits metastasis and epithelial to mesenchymal transition of lung adenocarcinoma via suppressing SOX4. , 2017, European review for medical and pharmacological sciences.

[71]  Jing Zhong,et al.  lncRNA-UCA1 enhances cell proliferation through functioning as a ceRNA of Sox4 in esophageal cancer. , 2016, Oncology reports.

[72]  J. Cigudosa,et al.  The SRY-HMG box gene, SOX4, is a target of gene amplification at chromosome 6p in lung cancer. , 2009, Human molecular genetics.

[73]  R. Boxtel,et al.  The role of SRY-related HMG box transcription factor 4 (SOX4) in tumorigenesis and metastasis: friend or foe? , 2013, Oncogene.

[74]  Hsin-Yi Huang,et al.  SOX4 Transcriptionally Regulates Multiple SEMA3/Plexin Family Members and Promotes Tumor Growth in Pancreatic Cancer , 2012, PloS one.

[75]  Jin Chen,et al.  MicroRNA-212 Inhibits Osteosarcoma Cells Proliferation and Invasion by Down-Regulation of Sox4 , 2014, Cellular Physiology and Biochemistry.

[76]  E. Lander,et al.  Local regulation of gene expression by lncRNA promoters, transcription and splicing , 2016, Nature.

[77]  Bingpeng Chen,et al.  MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by targeting SOX4 , 2017, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[78]  M. Nieto.  Epithelial-Mesenchymal Transitions in development and disease: old views and new perspectives. , 2009, The International journal of developmental biology.

[79]  Fengbo Tan,et al.  Increased expression of SOX4 is associated with colorectal cancer progression , 2016, Tumor Biology.

[80]  Feng-Hou Gao,et al.  MicroRNA-191 promotes pancreatic cancer progression by targeting USP10 , 2014, Tumor Biology.

[81]  Y. Yatabe,et al.  Reduced Expression of the let-7 MicroRNAs in Human Lung Cancers in Association with Shortened Postoperative Survival , 2004, Cancer Research.

[82]  V. P. Chuprina,et al.  Solution Structure of the Sequence-specific HMG Box of the Lymphocyte Transcriptional Activator Sox-4 (*) , 1995, The Journal of Biological Chemistry.

[83]  A. Brenner,et al.  Phase I study of MRX34, a liposomal miR-34a mimic, administered twice weekly in patients with advanced solid tumors , 2017, Investigational New Drugs.

[84]  Elaine Fuchs,et al.  Defining the impact of beta-catenin/Tcf transactivation on epithelial stem cells. , 2005, Genes & development.

[85]  Jian Zhao,et al.  MicroRNA-539 inhibits colorectal cancer progression by directly targeting SOX4. , 2018, Oncology letters.

[86]  D. Long,et al.  MiR-381 inhibits migration and invasion in human gastric carcinoma through downregulatedting SOX4. , 2017, Oncology letters.

[87]  D. Baltimore,et al.  The microRNA-212/132 cluster regulates B cell development by targeting Sox4 , 2015, The Journal of experimental medicine.

[88]  Liang Zhao,et al.  MicroRNA-187, a downstream effector of TGFβ pathway, suppresses Smad-mediated epithelial-mesenchymal transition in colorectal cancer. , 2016, Cancer letters.

[89]  Xiao-lan Li,et al.  MiR-363-3p inhibits the epithelial-to-mesenchymal transition and suppresses metastasis in colorectal cancer by targeting Sox4. , 2016, Biochemical and biophysical research communications.

[90]  C. Andl,et al.  SOX4 interacts with EZH2 and HDAC3 to suppress microRNA-31 in invasive esophageal cancer cells , 2015, Molecular Cancer.

[91]  M. Manns,et al.  The microRNA-449 family inhibits TGF-β-mediated liver cancer cell migration by targeting SOX4. , 2017, Journal of hepatology.

[92]  Wei Li,et al.  SOX4 overexpression is a novel biomarker of malignant status and poor prognosis in breast cancer patients , 2015, Tumor Biology.

[93]  Kevin Struhl,et al.  An Epigenetic Switch Involving NF-κB, Lin28, Let-7 MicroRNA, and IL6 Links Inflammation to Cell Transformation , 2009, Cell.

[94]  T. Ørntoft,et al.  Dysregulation of the transcription factors SOX4, CBFB and SMARCC1 correlates with outcome of colorectal cancer , 2009, British Journal of Cancer.

[95]  C. Moreno.  The Sex-determining region Y-box 4 and homeobox C6 transcriptional networks in prostate cancer progression: crosstalk with the Wnt, Notch, and PI3K pathways. , 2010, The American journal of pathology.

[96]  M. Nieto,et al.  The Snail genes as inducers of cell movement and survival: implications in development and cancer , 2005, Development.

[97]  Jørgen Kjems,et al.  Genomic profiling of microRNAs in bladder cancer: miR-129 is associated with poor outcome and promotes cell death in vitro. , 2009, Cancer research.

[98]  M. Kassem,et al.  microRNA-320/RUNX2 axis regulates adipocytic differentiation of human mesenchymal (skeletal) stem cells , 2014, Cell Death and Disease.

[99]  J. Stenvang,et al.  Silencing of microRNA families by seed-targeting tiny LNAs , 2011, Nature Genetics.

[100]  Kevin Kalinsky,et al.  AKT in cancer: new molecular insights and advances in drug development , 2016, British journal of clinical pharmacology.

[101]  Michael L. Gatza,et al.  Amplification of SOX4 promotes PI3K/Akt signaling in human breast cancer , 2017, Breast Cancer Research and Treatment.

[102]  Joshua D. Smith,et al.  De Novo SOX4 Variants Cause a Neurodevelopmental Disease Associated with Mild Dysmorphism. , 2019, American journal of human genetics.

[103]  S. Kauppinen,et al.  Therapeutic Silencing of MicroRNA-122 in Primates with Chronic Hepatitis C Virus Infection , 2010, Science.

[104]  C. Croce,et al.  MicroRNA-cancer connection: the beginning of a new tale. , 2006, Cancer research.

[105]  R. van Boxtel,et al.  SOX4 Mediates TGF-β-Induced Expression of Mesenchymal Markers during Mammary Cell Epithelial to Mesenchymal Transition , 2013, PloS one.

[106]  Xiaoyi Duan,et al.  Long non-coding RNA ABHD11-AS1 promotes colorectal cancer development through regulation of miR-133a/SOX4 axis , 2018, Bioscience reports.

[107]  C. Croce,et al.  Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[108]  S. Tavazoie,et al.  TMEM2 Is a SOX4-Regulated Gene That Mediates Metastatic Migration and Invasion in Breast Cancer. , 2016, Cancer research.

[109]  Thomas A Milne,et al.  MLL targets SET domain methyltransferase activity to Hox gene promoters. , 2002, Molecular cell.

[110]  Gordon B. Mills,et al.  Phosphorylation of β-Catenin by AKT Promotes β-Catenin Transcriptional Activity* , 2007, Journal of Biological Chemistry.

[111]  Helin Zhang,et al.  MiR-133a suppresses the migration and invasion of esophageal cancer cells by targeting the EMT regulator SOX4. , 2015, American journal of translational research.

[112]  Yang Cao,et al.  LncRNA‐PAGBC acts as a microRNA sponge and promotes gallbladder tumorigenesis , 2017, EMBO reports.

[113]  V. Lefebvre,et al.  The transcription factor Sox4 is a downstream target of signaling by the cytokine TGF-β and suppresses TH2 differentiation , 2012, Nature Immunology.

[114]  Y. You,et al.  Upregulated Expression of SOX4 Is Associated with Tumor Growth and Metastasis in Nasopharyngeal Carcinoma , 2015, Disease markers.

[115]  D. Pisano,et al.  Sox4 Links Tumor Suppression to Accelerated Aging in Mice by Modulating Stem Cell Activation , 2014, Cell reports.

[116]  Jorng-Tzong Horng,et al.  Identification of SOX4 target genes using phylogenetic footprinting-based prediction from expression microarrays suggests that overexpression of SOX4 potentiates metastasis in hepatocellular carcinoma , 2008, Oncogene.

[117]  X. Yang,et al.  SOX4 is associated with poor prognosis in prostate cancer and promotes epithelial–mesenchymal transition in vitro , 2013, Prostate Cancer and Prostatic Disease.

[118]  Dong Chen,et al.  DownRegulated SOX4 Expression Suppresses Cell Proliferation, Migration, and Induces Apoptosis in Osteosarcoma In Vitro and In Vivo , 2017, Calcified Tissue International.

[119]  Pengbo Liu,et al.  Sex-determining region Y box 4 is a transforming oncogene in human prostate cancer cells. , 2006, Cancer research.

[120]  Ying-yu Jin,et al.  MicroRNA-338-3p functions as tumor suppressor in breast cancer by targeting SOX4. , 2015, International journal of oncology.

[121]  D. Reinberg,et al.  Histone methyltransferase activity associated with a human multiprotein complex containing the Enhancer of Zeste protein. , 2002, Genes & development.

[122]  B. Han,et al.  Metformin inhibits epithelial-mesenchymal transition in prostate cancer cells: involvement of the tumor suppressor miR30a and its target gene SOX4. , 2014, Biochemical and biophysical research communications.

[123]  F. Liu,et al.  MicroRNA-138 attenuates epithelial-to-mesenchymal transition by targeting SOX4 in clear cell renal cell carcinoma. , 2017, American journal of translational research.

[124]  M. Kassem,et al.  Genome-wide mRNA and miRNA expression profiling reveal multiple regulatory networks in colorectal cancer , 2015, Cell Death and Disease.

[125]  Z. Su,et al.  SOX4 induces tumor invasion by targeting EMT-related pathway in prostate cancer , 2017, Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine.

[126]  G. Basso,et al.  The lncRNA CASC15 regulates SOX4 expression in RUNX1-rearranged acute leukemia , 2017, Molecular Cancer.

[127]  D. Bailey,et al.  Safety and activity of microRNA-loaded minicells in patients with recurrent malignant pleural mesothelioma: a first-in-man, phase 1, open-label, dose-escalation study. , 2017, The Lancet. Oncology.

[128]  P. Zhu,et al.  LncSox4 promotes the self-renewal of liver tumour-initiating cells through Stat3-mediated Sox4 expression , 2016, Nature Communications.

[129]  Chensheng Qiu,et al.  Upregulation of microRNA-25-3p inhibits proliferation, migration and invasion of osteosarcoma cells in vitro by directly targeting SOX4. , 2017, Molecular medicine reports.

[130]  K. Tao,et al.  miR-191 promotes tumorigenesis of human colorectal cancer through targeting C/EBPβ , 2014, Oncotarget.

[131]  R. Kulshreshtha,et al.  P53-miR-191-SOX4 regulatory loop affects apoptosis in breast cancer , 2017, RNA.

[132]  B. Davis-Dusenbery,et al.  MicroRNA in Cancer: The Involvement of Aberrant MicroRNA Biogenesis Regulatory Pathways. , 2010, Genes & cancer.

[133]  X. Yuan,et al.  SOX4 is a potential prognostic factor in human cancers: a systematic review and meta-analysis , 2015, Clinical and Translational Oncology.

[134]  Gang Li,et al.  Pleiotropic function of SRY-related HMG box transcription factor 4 in regulation of tumorigenesis , 2012, Cellular and Molecular Life Sciences.

[135]  Jingqin Luo,et al.  Epigenetic repression of microRNA-129-2 leads to overexpression of SOX4 oncogene in endometrial cancer. , 2009, Cancer research.

[136]  Shaohua Zhang,et al.  MicroRNA-212 functions as a tumor-suppressor in human non-small cell lung cancer by targeting SOX4. , 2017, Oncology reports.

[137]  B. Han,et al.  MicroRNA‐132/212 Upregulation Inhibits TGF‐β‐Mediated Epithelial–Mesenchymal Transition of Prostate Cancer Cells by Targeting SOX4 , 2016, The Prostate.

[138]  Jianhua Fu,et al.  SOX4 arrests lung development in rats with hyperoxia-induced bronchopulmonary dysplasia by controlling EZH2 expression , 2017, International journal of molecular medicine.

[139]  C. Moreno,et al.  Wnt signaling blockage inhibits cell proliferation and migration, and induces apoptosis in triple-negative breast cancer cells , 2013, Journal of Translational Medicine.