UNASSIGNED: The transcription factor, SOX13 is part of the SOX family. SOX proteins are crucial in the progression of many cancers, and some correlate with carcinogenesis. Nonetheless, the biological and clinical implications of SOX13 in human breast cancer (BC) remain rarely known.
UNASSIGNED: We evaluated the survival and expression data of SOX13 in BC patients via the UNLCAL, GEPIA, TIMER, and Kaplan-Meier plotter databases. Immunohistochemistry (IHC) was used to verify clinical specimens. The gene alteration rates of SOX13 were acquired on the online web cBioportal. With the aid of the TCGA data, the association between SOX13 mRNA expression and copy number alterations (CNA) and methylation was determined. LinkedOmics was used to identify the genes that co-expressed with SOX13 and the regulators. Immune infiltration and tumor microenvironment evaluations were assessed by ImmuCellAI and TIMER2.0 databases. SOX13 correlated drug resistance analysis was performed using the GDSC2 database.
UNASSIGNED: Higher SOX13 expression was discovered in BC tissues in comparison to normal tissues. Moreover, increased gene mutation and amplification of SOX13 were found in BC. Patients with increased SOX13 expression levels showed worse overall survival (OS). Cox analysis showed that SOX13 independently served as a prognostic indicator for poor survival in BC. Further, the expression of SOX13 was also confirmed to be correlated with tumor microenvironment and diverse infiltration of immune cells. In terms of drug sensitivity analysis, we found higher expression level of SOX13 predicts a high IC50 value for most of 198 drugs which predicts drug resistance.
UNASSIGNED: The present findings demonstrated that high expression of SOX13 negatively relates to prognosis and SOX13 plays an important role in cancer immunity. Therefore, SOX13 may potentially be adopted as a biomarker for predicting BC prognosis and infiltration of immune cells.

UNASSIGNED: It has been reported that long non-coding RNA THAP9-AS1 exerts carcinogenic role by mediating miRNAs and target genes in various human cancers. However, whether THAP9-AS1 influences the progression of nasopharyngeal carcinoma (NPC) remains unknown.
UNASSIGNED: The transcriptional levels of THAP9-AS1 and miR-185-5p were estimated via quantitative real time polymerase chain reaction (qRT-PCR) assay. The protein level of SOX13 was detected with western blotting assay. Additionally, methyl thiazolyl tetrazolium (MTT) assay as well as colony formation assay were utilized to measure cell growth. The apoptotic cells were observed by employing Terminal-deoxynucleoitidyl Transferase Mediated Nick End Labeling (TUNEL) staining analysis, and transwell assay was introduced to test cell migration in addition to invasion. Moreover, the relationship between miR-185-5p and THAP9-AS1 or SOX13 was estimated through dual-luciferase reporter gene assay.
UNASSIGNED: THAP9-AS1 was overexpressed in head and neck squamous cell carcinoma (HNSCC) tissues and NPC cells. Besides, silencing of THAP9-AS1 depressed the life processes of NPC cells including cell growth, migration as well as invasion but facilitated cell apoptosis. Further investigation proved that miR-185-5p was the direct target of THAP9-AS1. Besides, the knockdown of THAP9-AS1 notably reduced the transcriptional level of miR-185-5p. Furthermore, THAP9-AS1 served as a sponge of miR-185-5p to modulate the expression of SOX13, which regulated the development of NPC cells.
UNASSIGNED: This work verified that THAP9-AS1 promoted NPC cell progression at least partly by mediating the miR-185-5p/SOX13 axis.

Hsa_circ_0071589 can exacerbate the malignant behavior of colorectal cancer (CRC) cells. However, its function in stemness and oxaliplatin (OXP) resistance of CRC cells remains unclear. To assess the function of hsa_circ_0071589 in stemness and OXP resistance of CRC cells. Western blotting and qRT-PCR were applied to assess protein and mRNA levels. The association between hsa_circ_0071589, miR-133b and SOX13 was explored via a correlation analysis. Sphere formation was used to assess cell stemness. Meanwhile, the viability of CRC cells and OXP-resistant CRC cells was evaluated with the MTT assay. Cell stemness marker (CD133) levels and apoptosis of CRC cells and OXP-resistant CRC cells were tested using flow cytometry. The ALDH level was investigated using the related detection kit. In addition, the association between hsa_circ_0071589 and miR-133b and SOX13 was investigated using the RIP and dual luciferase assay. Finally, in vivo experiments were performed to detect the function of hsa_circ_0071589 in CRC, and the levels of SOX13, Ki67, and CD44 in mice were evaluated via immunohistochemistry staining. The expression of hsa_circ_0071589 and SOX13 was upregulated in CRC, whereas the expression of miR-133b was downregulated. Hsa_circ_0071589 knockdown significantly inhibited CRC stemness via the mediation of miR-133b. Moreover, hsa_circ_0071589 silencing significantly sensitized CRC cells to OXP by upregulating miR-133b. SOX13 was the direct target of miR-133b, and miR-133b could attenuate stemness and OXP resistance in CRC cells by targeting SOX13. Notably, hsa_circ_0071589 knockdown inhibited tumor growth and decreased OXP resistance in mice with CRC. Hsa_circ_0071589 aggravates stemness and OXP resistance by sponging miR-133b to indirectly target SOX13 in CRC. Thus, our study might present a novel treatment strategy against OXP-resistant CRC.

Breast cancer is the most frequent cancer among women and the second highest mortality in female across the world. Recent studies have illustrated that sex-determining region Y (SRY)-box protein (SOX) family plays essential roles in regulating various cancers. Nevertheless, the detailed effects of SOX13 on breast cancer are still uncovered. In our present study, SOX13 protein level was measured by using western blot assay in tissues and cells, and the results showed that SOX13 was upregulated in breast cancer tissues and cells compared with normal samples. Moreover, silencing SOX13 inhibited breast cancer cell viability, arrested cell cycle at G1/S phase and suppressed glycolysis, while overexpression of SOX13 reversed these events. Additionally, SOX13 knockdown reduced the level of proteins related to Wnt/β-catenin signaling pathway, whereas overexpression of tripartite motif containing 11 (TRM11) efficiently attenuated the effects, indicating that SOX13 controlled Wnt/β-catenin pathway depending on TRIM11. Furthermore, the data gained from xenograft tumor model illustrated that silencing SOX13 suppressed the tumor growth in nude mice and the glycolysis of tissues. In conclusion, our investigation illustrated that SOX13 facilitated breast cancer cell proliferation and glycolysis by modulating Wnt/β-catenin signaling pathway affected via TRIM11.

Sex-determining region Y (SRY)-related high mobility group (HMG) box (SOX) proteins are pivotal transcriptional factors that play essential roles in embryonic development, cell fate decisions and cancer development. The molecular mechanism of SOX13, a member of the SOX family, in hepatocellular carcinoma (HCC) remains largely unknown. In the current study, we found that HCC cells were able to form spheroids in serum-free suspension culture and that SOX13 expression was upregulated in spheroids enriched for cancer stem cells (CSCs). Inhibition of SOX13 in HCC-LM3 and MHCC-97H cells decreased the expression of stemness-related genes; attenuated spheroid formation, anchor-dependent and anchor-independent cell proliferation and tumorigenicity; and enhanced sensitivity to drug treatment. Furthermore, based on analysis of TCGA dataset, the results indicated that SOX13 expression was obviously upregulated and closely associated with poor prognosis in HCC patients. Moreover, SOX13 was correlated with TAZ and CD24 expression. These data strongly demonstrated that SOX13 is involved in maintaining cancer stem-like properties in HCC cells and plays a critical role in HCC development.

BACKGROUND: Long non-coding RNAs (lncRNAs) play crucial roles in the regulation and treatment of multiple myeloma (MM). The objective of this research was to study the functional mechanism of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) in MM.
METHODS: MALAT1, microRNA-1271-5p (miR-1271-5p), and SRY-Box 13 (SOX13) levels were examined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability, apoptosis, and invasion were respectively assayed using 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide (MTT), flow cytometry, and transwell assay. Glycolysis was evaluated by glucose consumption, lactate production, ATP/ADP ratio, and the detection of related enzymes. Associated proteins were measured using Western blot. Target relation was verified via dual-luciferase reporter assay. Xenograft tumor assay was implemented to study the influence of MALAT1 on MM in vivo.
RESULTS: The up-regulation of MALAT1 and the down-regulation of miR-1271-5p were found in MM serums and cells. MALAT1 knockdown suppressed cell viability, invasion, and glycolysis while expedited cell apoptosis in MM cells. MALAT1 directly targeted miR-1271-5p and miR-1271-5p depression reverted the effects of MALAT1 knockdown on MM cells. SOX13 was a target of miR-1271-5p and SOX13 overexpression weakened the effects of miR-1271-5p on MM. MALAT1 indirectly modulated SOX13 expression through targeting miR-1271-5p. MALAT1 down-regulation inhibited MM growth by miR-1271-5p/SOX13 axis in vivo.
CONCLUSIONS: LncRNA MALAT1 expedited MM tumorigenesis, invasion, and glycolysis via miR-1271-5p/SOX13 axis. MALAT1 might contribute to the therapy of MM as a promising indicator.

Aberrant expression of forkhead box C1 (FOXC1) promotes tumor metastasis in multiple human malignant tumors. However, the upstream modulating mode and downstream molecular mechanism of FOXC1 in metastasis of colorectal cancer (CRC) remain unclear. Herein we describe a systematic analysis of FOXC1 expression and prognosis in CRC performed on our clinical data and public databases, which indicated that FOXC1 upregulation in CRC samples was significantly associated with poor prognosis. FOXC1 knockdown inhibited migration and invasion, whereas FOXC1 overexpression caused the opposite phenotype in vitro and in vivo. Furthermore, MMP10, SOX4 and SOX13 were verified as the target genes of FOXC1 for promoting CRC metastasis. MMP10 was demonstrated as the direct target and mediator of FOXC1. Interestingly, Ser241 and Ser272 of FOXC1 were identified as the key sites to interact with p38 and phosphorylation, which were critically required for maintaining the stability of FOXC1 protein. Moreover, FOXC1 was dephosphorylated by protein phosphatase 2A and phosphorylated by p38, which maintained FOXC1 protein stability through inhibiting ubiquitination. Expression of p38 was correlated with FOXC1 and MMP10 expression, indirectly indicating that FOXC1 was regulated by p38 MAPK. Therefore, FOXC1 is strongly suggested as a pro-metastatic gene in CRC by transcriptionally activating MMP10, SOX4 and SOX13; p38 interacts with and phosphorylates the Ser241 and ser272 sites of FOXC1 to maintain its stability by inhibiting ubiquitination and degradation. In conclusion, the protein stability of FOXC1 mediated by p38 contributes to the metastatic effect in CRC. © 2019 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

The SRY-related high-mobility-group box (Sox) gene family encodes a set of transcription factors and is defined by the presence of highly conserved domains. The Sox gene can be divided into 10 groups (A-J). The SoxD subpopulation consists of Sox5, Sox6, Sox13 and Sox23, which are involved in the transcriptional regulation of developmental processes, including embryonic development, nerve growth and cartilage formation. Recently, the SoxD gene family was recognized as important transcriptional regulators associated with many types of cancer. In addition, Sox5 and Sox6 are representatives of the D subfamily, and there are many related studies; however, there are few reports on Sox13 and Sox23. In this review, we first introduce the structures of the SoxD genes. Next, we summarize the latest research progress on SoxD in various types of cancer. Finally, we discuss the potential direction of future SoxD research. In general, the information reviewed here may contribute to future experimental design and increase the potential of SoxD as a cancer treatment target.

PAX8 is identified as a regulator in the pathogenesis of human tumours and an indicator of the prognosis for patients. However, the role of PAX8 on proliferation in gastric cancer have not been studied. This study was aimed to explore the expression pattern of PAX8 in gastric cancer, and investigate the effect of PAX8 on the proliferation of gastric cancer cells. PAX8 and SOX13 were identified to be synchronously up-regulated in primary gastric cancer in human gastric cancer tissues and the gastric cancer datasets of TCGA, and gastric cancer patients of combined high PAX8 and SOX13 expression showed poor prognosis. Furthermore, SOX13 can mediate PAX8 and its targeted genes, Aurora B and Cyclin B1, expression in AGS and MGC803 cell lines. Flow cytometry and EdU incorporation assays showed that silencing PAX8 can block the cell cycle of gastric cancer cell in G1 phase and SOX13 expression can rescue the arrested proliferative process induced by PAX8 silenced in CCK8 and colony formation assays. Thus, combined SOX13 and PAX8 expression regulate the proliferation of gastric cancer cells, and both SOX13 and PAX8 play an oncogene function in gastric cancer.

BACKGROUND: Angiogenesis plays a critical role in the progression of glioma. Previous studies have indicated that RNA-binding proteins (RBPs) interact with RNAs and participate in the regulation of the malignant behaviors of tumors. As a type of endogenous non-coding RNAs, circular RNAs (circRNAs) are abnormally expressed in various cancers and are involved in diverse tumorigeneses including angiogenesis.
METHODS: The expression levels of FUS, circ_002136, miR-138-5p, SOX13, and SPON2 were determined using quantitative real-time PCR (qRT-PCR) and western blot. Transient cell transfection was performed using the Lipofectamine 3000 reagent. The RNA-binding protein immunoprecipitation (RNA-IP) and the RNA pull-down assays were used to detect the interaction between FUS and circ_002136. The dual-luciferase reporter assay system was performed to detect the binding sites of circ_002136 and miR-138-5p, miR-138-5p and SOX13. The chromatin immunoprecipitation (ChIP) assays were used to examine the interactions between transcription factor SOX13 and its target proteins .
RESULTS: We demonstrated that down-regulation of FUS or circ_002136 dramatically inhibited the viability, migration and tube formation of U87 glioma-exposed endothelial cells (GECs). MiR-138-5p was down-regulated in GECs and circ_002136 functionally targeted miR-138-5p in an RNA-induced silencing complex (RISC). Inhibition of circ_002136, combined with the restoration of miR-138-5p, robustly reduced the angiogenesis of GECs. As a target gene of miR-138-5p, SOX13 was overexpressed in GECs and was proved to be involved in circ_002136 and miR-138-5p-mediated angiogenesis in gliomas. In addition, we found that SOX13 was directly associated with and activated the SPON2 promoter, thereby up-regulating the expression of SPON2 at the transcriptional level. Knockdown of SPON2 suppressed the angiogenesis in GECs. More important, SOX13 activated the FUS promoter and increased its expression, forming a feedback loop.
CONCLUSIONS: Our data suggests that the feedback loop of FUS/circ_002136/miR-138-5p/SOX13 played a crucial role in the regulation of angiogenesis in glioma. This also provides a potential target and an alternative strategy for combined glioma therapy.