Downregulation of SOX11 in fetal heart tissue, under hyperglycemic environment, mediates cardiomyocytes apoptosis.

Gestational diabetes mellitus is one of the causes of abnormal embryonic heart development, but the mechanism is still poor. This study investigated the regulatory mechanism and role of SOX11 in congenital heart abnormality in a hyperglycemic environment. Immunohistochemistry, Western blotting, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) showed decreased SOX11 protein and messenger RNA (mRNA) levels in the heart tissue of diabetic offspring compared with the control group. A Sequenom EpiTYPER MassArray showed that methylation sites upstream in SOX11 region 1 were increased in the diabetic group compared with the control group. Luciferase reporter assays and qRT-PCR showed that Dnmt3b overexpression decreased SOX11 promoter activity and its mRNA level, whereas Dnmt3a had little effect on regulating SOX11 expression. Furthermore, we found that Dnmt3L cooperated with Dnmt3b to regulate SOX11 gene expression. Additionally, the function of SOX11 silencing was analyzed by using small interfering RNA-mediated knockdown. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and apoptotic assays showed that SOX11 downregulation inhibited cell viability and induced apoptosis in cardiomyocytes. Overexpression of the SOX11 gene suppressed cardiomyocytes apoptosis after high glucose treatment. We identified a novel epigenetic regulatory mechanism of SOX11 during heart development in a hyperglycemic environment and revealed a distinct role of SOX11 in mediating cardiomyocytes viability and apoptosis.

Circular RNA THBS1 promotes proliferation and apoptosis of non-small cell lung cancer cells by sponging miR-129-5p and regulating SOX4 expression.

PURPOSE: To investigate the influence of circular ribonucleic acid thrombospondin-1 (circTHBS1) on the proliferation and apoptosis of non-small cell lung cancer (NSCLC) cells by sponging miR-129-5p and regulating the expression of SRY-box transcription factor 4 (SOX4). METHODS: Carcinoma and para-carcinoma specimens were collected from 40 NSCLC patients, and 25 pairs of specimens were obtained from patients with metastatic and non-metastatic NSCLC. After NSCLC cells were cultured, the proliferation was detected via cell counting kit-8 (CCK-8) and 5-Ethynyl-2'- deoxyuridine (EdU) assays, and the cell cycle and apoptosis rate were analyzed through flow cytometry. Finally, the action targets of circTHBS1 were determined using dual-luciferase reporter gene assay, and Western blotting assay was applied to measure the changes in protein levels. RESULTS: The expression of circTHBS1 was markedly higher in NSCLC patients than that in control group, and it was increased in patients with metastatic NSCLC compared with that in patients with non-metastatic NSCLC. Moreover, the proliferative ability of the cells was weakened notably after transfection with small interfering (Si)-CircTHBS1, but it was enhanced remarkably after transfection with CircTHBS1-overexpression vector (OE). There were complementary sites in circTHBS1 for the 3'-UTR of miR-129-5p, and the fluorescence intensity of wild-type circTHBS1 declined evidently after interacting with miR-129-5p. Besides, there was a putative binding site between miR-129-5p and SOX4, and SOX4 expression was decreased obviously after overexpressing miR-129-5p but increased following overexpression of circTHBS1. CONCLUSIONS: CircTHBS1 promotes the proliferation and inhibits the apoptosis of NSCLC cells through targeting miR-129-5p and regulating SOX4 expression.

MicroRNA-92a Inhibits the Cell Viability and Metastasis of Prostate Cancer by Targeting SOX4.

MicroRNAs (miRNAs) was confirmed to play an active role in the pathogenesis of prostate cancer (PCa). The expression and biological function for miR-92a in PCa remains unknown. In this study, we demonstrated that miR-92a expression was decreased in PCa tissues and cells lines. Overexpression miR-92a inhibited the cell viability, migration and invasion of PC-3 while inhibition of miR-92a led to opposite alteration of cell viability and metastasis of DU-145 cells. Mechanically, we confirmed that miR-92a interacted with 3'-UTR of SOX4 through the complementary sequences by luciferase reporter assay. qRT-PCR and western blot confirmed that miR-92a inhibited the expression of SOX4 in PCa cells. Moreover, overexpression of SOX4 reversed the inhibitory effects of miR-92a overexpression on PC-3 cell viability, migration and invasion, while knockdown of SOX4 suppressed the promoting effects of miR-92a knockdown on these biological functions of DU-145 cells. Therefore, our study indicates that miR-92a inhibits the growth and metastasis of prostate cancer by targeting SOX4, and can potentially serve as a biomarker and treatment target for PCa patients.

MiR-214 regulates fracture healing through inhibiting Sox4 and its mechanism.

OBJECTIVE: To investigate the expression of micro ribonucleic acid (miR)-214 in the bone tissue and blood of patients with fragility fracture. METHODS: The expression of miR-214 was detected via quantitative reverse transcription-polymerase chain reaction. The effect of miR-214 on proliferation and apoptosis of osteoblasts were detected via methyl thiazolyl tetrazolium assay and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling staining. RESULTS: The expression of miR-214 in the bone tissue and blood of patients with fragility fracture significantly declined. miR-214 could promote the proliferation of osteoblasts and inhibited the apoptosis of osteoblasts. miR-214 is involved in fracture healing through inhibiting Sox4 and promoting phosphorylation of PI3K/AKT pathway. The expression of BSP in cells treated with miR-214 mimics was significantly increased to 2.5-fold (p=0.0168), while the expression of BSP in cells treated with miR-214 AMO was significantly decreased, reduced to 0.3 times (p=0.0397). The expression of BMP2 in cells treated with miR-214 mimics was significantly increased to 2.5-fold (p=0.003), while the expression of BMP2 was significantly decreased in cells treated with miR-214 AMO, reduced to 0.3 times (p=0.0002). miR-214 can regulate the expression of Sox2, PI3K and AKT proteins. CONCLUSION: MiR-214 regulates the proliferation, apoptosis, bone formation of osteoblasts and participate in the fracture healing process by inhibiting the expression of Sox4, which provided new ideas for clinical treatment of fracture healing.

Molecular Pathogenesis of Mantle Cell Lymphoma.

Mantle cell lymphoma (MCL) is a mature B-cell neoplasm with heterogeneous clinical behavior molecularly characterized by the constitutive overexpression of cyclin D1 and deregulation of different signaling pathways. SOX11 expression determines an aggressive phenotype associated with accumulation of many chromosomal alterations and somatic gene mutations. A subset of patients with the SOX11-negative leukemic non-nodal MCL subtype follows an initial indolent clinical evolution and may not require treatment at diagnosis, although eventually may progress to an aggressive disease. We discuss the genetic and molecular alterations with impact on the cancer hallmarks that characterize the lymphomagenesis of the 2 MCL subtypes.

LncRNA FAL1 Upregulates SOX4 by Downregulating miR-449a to Promote the Migration and Invasion of Cervical Squamous Cell Carcinoma (CSCC) Cells.

This study aimed to investigate the role of lncRNA FAT1 in cervical squamous cell carcinoma (CSCC). We found that FAT1 was upregulated in CSCC tissues. The expression of FAT1 was not affected by clinical stages. High levels of FAT1 predicted poor survival. The expression of miR-449a was inversely correlated with the expression of FAT1. SOX4 mRNA expression was positively correlated with the expression of FAT1 in CSCC tissues. FAT1 over-expression led to an upregulated SOX4 expression and downregulated miR-449a expression. MiR-449a over-expression failed to affect FAT1 expression but downregulated SOX4 expression. FAT1 and SOX4 over-expression led to increased rates of CSCC cell migration and invasion, miR-449a over-expression led to decreased rates of CSCC cell migration and invasion and attenuated the effects of SOX4 over-expression. Therefore, FAL1 can upregulate SOX4 by downregulating miR-449a to promote the migration and invasion of CSCC cells.

SOX4 is activated by C-MYC in prostate cancer.

Although MYC proto-oncogene (C-MYC) amplification has been consistently reported to be a potential marker for prostate cancer (PCa) progression and prognosis, the clinicopathological and prognostic significance of C-MYC protein expression remains controversial. Overexpression of SOX4 has been shown to play important roles in multiple cancers including PCa. However, the link between these two critical genetic aberrations is unclear. In the current study, we showed that C-MYC was overexpressed in 16.2% (17/105) of Chinese patients with localized PCa. Overexpression of C-MYC was significantly associated with high Gleason scores (P = 0.012) and high Ki67 labeling index (P = 0.005). C-MYC overexpression was correlated with cancer-related mortality and suggested to be an unfavorable prognostic factor in Chinese PCa patients (P = 0.018). Overexpression of C-MYC is associated with SOX4 overexpression in PCa tissues. Notably, SOX4 is a direct target gene of C-MYC; C-MYC activates SOX4 expression via binding to its promoter. In addition, Co-IP analysis demonstrated a physical interaction between C-MYC and SOX4 protein in PCa cells. Clinically, C-MYC+/SOX4+ characterized poor prognosis in a subset of PCa patients. In total, C-MYC overexpression may contribute to PCa progression by activating SOX4. Our findings highlight an important role of C-MYC/SOX4 in PCa progression in a subset of PCa patients.

Long non-coding RNA OR3A4 is associated with poor prognosis of human non-small cell lung cancer and regulates cell proliferation via up-regulating SOX4.

OBJECTIVE: Recent studies have uncovered that long noncoding RNAs (lncRNAs) play a crucial role in the progression of malignant tumors. Non-small cell lung cancer (NSCLC) is a common type of fatal cancer worldwide. The aim of this study was to identify the specific function of lncRNA OR3A4 in the progression of NSCLC, and to explore the possible underlying mechanism. PATIENTS AND METHODS: LncRNA OR3A4 expression in 52-paired NSCLC tissues and adjacent normal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation assay and cell apoptosis assay were used to investigate the function of OR3A4 in NSCLC. Furthermore, the underlying mechanism was explored by qRT-PCR and Western blot assay. RESULTS: OR3A4 expression was remarkably upregulated in NSCLC tissues when compared with adjacent normal tissues. The overall survival of NSCLC patients in high OR3A4 expression group was significantly worse than those in low OR3A4 expression group. After the silence of OR3A4, the proliferation of NSCLC cells was significantly inhibited. Besides, the apoptosis of NSCLC cells was remarkably promoted after the silence of OR3A4. Meanwhile, knockdown of OR3A4 significantly down-regulated the mRNA and protein levels of SOX4 in NSCLC cells. Furthermore, the expression of SOX4 was found upregulated in both NSCLC tissues and cells. CONCLUSIONS: These above results suggested that OR3A4 could promote cell proliferation and suppress cell apoptosis in NSCLC through up-regulating SOX4. Our findings demonstrated that OR3A4 might serve as a new therapeutic intervention for NSCLC patients.

SOX11 expression in a case of papillary thyroid carcinoma with fibromatosis/fasciitis-like stroma containing BRAF c.1799_1801delTGA and CTNNB1 c.133T>C mutations.

We describe a case of papillary thyroid carcinoma with fibromatosis/fasciitis-like stroma (PTC-FLS) that contained the rare BRAF c.1799_1801delTGA (p.V600_K601delinsE) mutation, which has not previously been reported in this tumour, as well as the CTNNB1 c.133T>C (p.S45P) mutation. We also report the novel observation that spindle cells of the mesenchymal component exhibit diffuse nuclear but not cytoplasmic expression of SOX11, whereas the malignant epithelial cells did not. This suggests that immunoreactivity for SOX11 can be an alternative diagnostic tool for evaluating cases of PTC-FLS where the nuclear expression of ß-catenin is ambiguous.

SOX11 regulates apoptosis and cell cycle in hepatocellular carcinoma via Wnt/ß-catenin signaling pathway.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer with high mortality. Identifying key molecules involved in the regulation of HCC development is of great clinical significance. SOX11 is a transcription factor belonging to group C of Sry-related high mobility group box family whose abnormal expression is frequently seen in many kinds of human cancers. Here, we noted that the expression of SOX11 was decreased in human HCC tumors compared with that in matched normal tissues. Overexpression of SOX11 promoted growth inhibition and apoptosis in HCC cell line HuH-7. Mechanistically, SOX11 enhanced the expression of nemo-like kinase and the phosphorylation of TCF4, thereby blunting the activation of oncogenic Wnt/ß-catenin signaling pathway in HuH-7 cells. Finally, SOX11 was also found to sensitize HuH-7 cells to chemotherapy drugs cisplatin and 5-fluorouraci. Therefore, our study identifies SOX11 as a potential tumor suppressor in HCC and may hopefully be beneficial for the clinical diagnosis or treatment of HCC.

miR­188 suppresses tumor progression by targeting SOX4 in pediatric osteosarcoma.

microRNA­188 (miR­188) acts as a tumor suppressor in various types of human cancer, including glioma, oral squamous cell carcinoma and hepatocellular carcinoma. However, the function and mechanism of miR­188 in pediatric osteosarcoma (OS) have yet to be investigated. In the present study reverse transcription­quantitative polymerase chain reaction revealed that miR­188 expression was significantly downregulated in pediatric OS tissues and cell lines. miR­188 overexpression markedly suppressed OS cell proliferation, migration and invasion, and induced cellular apoptosis. An in vivo assay demonstrated that miR­188 overexpression inhibited tumor growth. miR­188 targeted SOX4 to regulate its expression. miR­188 expression was inversely correlated with SOX4 in pediatric OS tissues. SOX4 restoration abrogated the inhibitory effects of miR­188 on OS cells. The results of the present study indicated that miR­188 suppressed pediatric OS progression by targeting SOX4.

SOX11 expression as a MRD molecular marker for MCL in comparison with t(11;14) and IGH rearrangement.

The main cause of death in mantle cell lymphoma (MCL) patients is relapse due to undetermined minimal residual disease (MRD) and therefore monitoring MRD is crucial for making the best treatment decisions. The gold standard method for MRD analysis is the quantitative polymerase chain reaction. The most commonly used molecular markers for measuring MRD in MCL are: t(11;14)(q13;p32) translocation or CCND1 expression and IGH rearrangement. Such markers can, however, be found in other B cell non-Hodgkin lymphomas. Recent studies demonstrate that SOX11 expression is highly specific for MCL and could be used as a marker for measuring MRD. Moreover, evidence shows that SOX11 level could be predictive for overall survival (OS) and progression-free survival (PFS). We have measured MRD level in follow-up samples from 27 patients diagnosed with MCL using the molecular markers: t(11;14), IGH rearrangement and SOX11 expression. We compared all markers by their sensitivity, utility and quantitative range. We also examined the predictive value of SOX11 expression for OS and PFS. SOX11 expression was found to have better specificity, quantitative range and utility than the t(11;14). The predictive value of SOX11 expression was confirmed. At diagnosis, patients with high SOX11 expression had shorter PFS than patients with low SOX11 expression (p = 0.04*); differences between OS being statistically insignificant. To our best knowledge this is a first study comparing SOX11 with t(11;14) and IGH rearrangement as markers of MRD level. Moreover, in this study we confirmed that SOX11 is useful in cases when other molecular markers cannot be used.

SOX12 upregulation is associated with metastasis of hepatocellular carcinoma and increases CDK4 and IGF2BP1 expression.

OBJECTIVE: In this study, we studied the expression profile of SOX12 gene in different pathological stages of hepatocellular carcinoma (HCC) and explored the possible downstream genes related to its regulation of HCC invasion and migration. MATERIALS AND METHODS: Bioinformatic data mining was performed in liver cancer cohort in TCGA. HepG2 cells were used as in vitro cell model to assess the effect of SOX12 on CDK4 and IGF2BP1 expression. The association between the expression of SOX12, CDK4 or IGF2BP1 and survival time in HCC patients was also assessed based on the data in TCGA. RESULTS: The regional lymph node metastasis (N1) and distant metastasis (M1) cases had significantly increased SOX12 expression than the lymph node negative (N0) and distant metastasis negative (M0) cases respectively. CDK4 and IGF2BP1 were among the top 20 SOX12 co-upregulated genes in HCC, which have well characterized enhancing the effect on HCC cell growth, invasion, and metastasis. In HepG2 cells, knockdown of SOX12 reduced IGF2BP1 and CDK4 expression, while enforced SOX12 expression significantly enhanced their expression. Low SOX12 or CDK4 expression was associated with significantly better 3-year survival and better 5-year survival. Low IGF2BP1 expression was associated with significantly better 3-year survival in HCC patients. CONCLUSIONS: SOX12 upregulation is associated with regional and distant metastasis of HCC. SOX12 can increase the expression of CDK4 and IGF2BP1, which confer malignant phenotypes to HCC. The expression of SOX12, IGF2BP1 or CDK4 might be potential clinical prognostic markers for HCC.

Overexpression of SOX4 correlates with poor prognosis of acute myeloid leukemia and is leukemogenic in zebrafish.

The SOX4 transcription factor is a key regulator of embryonic development, cell-fate decision, cellular differentiation and oncogenesis. Abnormal expression of SOX4 is related to malignant tumor transformation and cancer metastasis. However, no reports are available regarding the clinical significance of SOX4 in acute myeloid leukemia (AML) and the role of SOX4 in leukemogenesis. In the current study, we found that AML patients with low bone marrow (BM) SOX4 expression had higher remission rates and longer overall survival than those with high SOX4 expression, regardless of age, white blood cell count at diagnosis, karyotype profile and NPM1/FLT3-ITD status. To elucidate the role of SOX4 in leukemogenesis, we generated a transgenic zebrafish model that overexpressed human SOX4 in the myeloid lineage Tg(spi1-SOX4-EGFP). These transgenic zebrafish showed, at 5 months of age, increased myelopoiesis with dedifferentiation in kidney marrow. At 9 months of age, their kidney structure was significantly effaced and distorted by increased infiltration of myeloid progenitor cells. These results suggest that SOX4 is not only an independent prognostic factor of AML, but also an important molecular factor in leukemogenesis.

MicroRNA-25 suppresses proliferation, migration, and invasion of osteosarcoma by targeting SOX4.

Altered expression of the miR-25 has been implicated in many human malignant progression as oncogene or tumor suppressor. However, the precise role of miR-25 in osteosarcoma progression remains largely unclear. This study aimed to investigate the role and underlying mechanism of miR-25 in osteosarcoma. In this study, we demonstrated that miR-25 was significantly downregulated in osteosarcoma cell lines and tissues and that lower miR-25 was associated with advanced tumor-node-metastasis stage and lymph node metastasis. Then, we found that introduction of miR-25 significantly suppressed the proliferation, colony formation, migration, and invasion of osteosarcoma cells in vitro and retarded tumor growth in vivo. Further studies indicated that the epithelial-mesenchymal transition-related transcription factor, SOX4 (SRY-related high-mobility group box 4), was a direct target gene of miR-25, evidenced by bioinformatics analysis predicted and luciferase reporter assay. Furthermore, miR-25 could decrease the expression of SOX4 levels and inhibited epithelial-mesenchymal transition process. The levels of miR-25 were inversely correlated with those of SOX4 expression in osteosarcoma tissues. SOX4 overexpression rescued miR-25-induced suppression of proliferation, migration, and invasion of osteosarcoma cells. Taken together, these results suggest that miR-25 functions as a tumor suppressor in the progression of osteosarcoma by repressing SOX4.

SOX4 induces tumor invasion by targeting EMT-related pathway in prostate cancer.

SOX4 (sex-determining region Y-related high-mobility group box 4) is associated with tumor progression and poor clinical outcome in several cancers. This study aims to evaluate whether SOX4 affects the biological behaviors of prostate cancer and further elucidate whether this effect works through the epithelial-mesenchymal transition pathway. We investigated the expression of SOX4 in a series of prostate cancer tissues and adjacent noncancerous tissues, as well as in a panel of prostate cancer cell lines. Cell proliferation, migration, and invasion were evaluated in SOX4 knockdown prostate cancer cell lines by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and Transwell assay. Our results showed that the expression of SOX4 was remarkably upregulated both in prostate cancer tissues and in cell lines. Knockdown of SOX4 repressed the ability of cell proliferation and migration of DU145 cells. Moreover, inhibition of SOX4 could reverse the epithelial-mesenchymal transition processes through upregulation of E-cadherin and downregulation of vimentin. This study provided evidence that SOX4 could serve as a potential therapeutic target in prostate cancer.

Expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma.

The aim of our study was to evaluate the immunohistochemical expression of SOX11, PAX5, TTF-1 and ISL-1 in medulloblastoma (MB) to investigate their diagnostic usefulness. METHODS: Immunohistochemical expression of PAX5 (two antibodies: Dako, DAK-Pax5; and BD, clone 24), TTF-1 (Dako, 8G7G3/1), SOX11 (CL0142; Abcam) and ISL-1 (1 H9, Abcam) was analyzed using the h-score and Remmele score in 25 cases of MB. RESULTS: There were 18 MBs of classic and 7 of desmoplastic type. SOX11 was strongly expressed in all tumors. The expression of PAX5 was higher and more frequent in a case of DAK-Pax5 clone (25/25) than clone 24 (6/25). ISL-1 was positive in 11 (44%) and TTF-1 in 3 (12%) cases. ISL-1 expression correlated positively (p<0.001), while TTF-1 correlated negatively with the age of patients (p=0.039). PAX5 expression correlated with ISL-1 (p=0.039) and showed a trend toward higher expression in the desmoplastic subtype (p=0.069). CONCLUSIONS: SOX11 is strongly and robustly expressed in MBs. PAX5 expression pattern differs substantially among two antibody clones. TTF-1 and ISL-1 is associated with the age of patients.

lncRNA-UCA1 enhances cell proliferation through functioning as a ceRNA of Sox4 in esophageal cancer.

Esophageal cancer (EC) is one of the most common gastrointestinal cancers, which leads to the sixth ranking of cancer-related death. Long non-coding RNAs (lncRNAs) play pivotal roles in many biological processes. lncRNA human urothelial carcinoma associated 1 (UCA1) is significantly upregulated and functions as an important oncogene in many types of human cancers. However, the role of UCA1 in EC and its underlying mechanism remains unclear. In the present study, we demonstrated that UCA1 was significantly upregulated in EC tissues and associated with poor prognosis. Overexpression of UCA1 promoted the proliferation of EC cells, while silence of UCA1 inhibited EC cells growth. Furthermore, we found that Sox4 was a direct target gene of UCA1. UCA1 regulated Sox4 expression through functioning as a competing endogenous RNA (ceRNA). UCA1 directly interacted with miR-204 and decreased the binding of miR-204 to Sox4 3'UTR, which suppressed the degradation of Sox4 mRNA by miR-204. This study provides the first evidence that UCA1 promotes cell proliferation through Sox4 in EC, suggesting that UCA1 and Sox4 may be potential therapeutic targets for EC.

Spatio-temporal expression of Sox genes in murine palatogenesis.

Members of the Sox gene family play critical roles in many biological processes including organogenesis. We carried out comparative in situ hybridisation analysis of seventeen Sox genes (Sox1-14, 17, 18 and 21) during murine palatogenesis from initiation to fusion of the palatal shelves above the dorsal side of the tongue. At palatal shelf initiation (E12.5), the localized expression of six Sox genes (Sox2, 5, 6, 9, 12 and 13) was observed in the shelves, whereas Sox4 and Sox11 showed ubiquitious expression. During the down-growth of palatal shelves (E13.5), Sox4, Sox5, and Sox9 exhibited restricted expression to the interior side of the palatal shelves facing the tongue. Following elevation of the palatal shelves (E14.5), Sox2, Sox11 and Sox21 expression was present in the midline epithelial seam. We thus identify dynamic spatio-temporal expression of Sox gene family during the process of palatogenesis.

SOXC and MiR17-92 gene expression profiling defines two subgroups with different clinical outcome in mantle cell lymphoma.

Mantle cell lymphoma (MCL) is a heterogeneous B-cell lymphoid malignancy where most patients follow an aggressive clinical course whereas others are associated with an indolent performance. SOX4, SOX11, and SOX12 belong to SOXC family of transcription factors involved in embryonic neurogenesis and tissue remodeling. Among them, SOX11 has been found aberrantly expressed in most aggressive MCL patients, being considered a reliable biomarker in the pathology. Several studies have revealed that microRNAs (miRs) from the miR-17-92 cluster are among the most deregulated miRNAs in human cancers, still little is known about this cluster in MCL. In this study we screened the transcriptional profiles of 70 MCL patients for SOXC cluster and miR17, miR18a, miR19b and miR92a, from the miR-17-92 cluster. Gene expression analysis showed higher SOX11 and SOX12 levels compared to SOX4 (P ≤ 0.0026). Moreover we found a negative correlation between the expression of SOX11 and SOX4 (P < 0.0001). miR17-92 cluster analysis showed that miR19b and miR92a exhibited higher levels than miR17 and miR18a (P < 0.0001). Unsupervised hierarchical clustering revealed two subgroups with significant differences in relation to aggressive MCL features, such as blastoid morphological variant (P = 0.0412), nodal presentation (P = 0.0492), CD5(+) (P = 0.0004) and shorter overall survival (P < 0.0001). Together, our findings show for the first time an association between the differential expression profiles of SOXC and miR17-92 clusters in MCL and also relate them to different clinical subtypes of the disease adding new biological information that may contribute to a better understanding of this pathology. © 2016 Wiley Periodicals, Inc.