Y-box-binding protein 1 mediates sorafenib resistance via the extracellular signal regulated-protein kinase pathway in hepatoma cells / 中华肝脏病杂志

Objective: To investigate the effect and possible mechanism of Y-box-binding protein 1 (YB-1) on sorafenib resistance in hepatoma cells. Methods: Lentiviral vectors with YB-1 overexpression and knockdown were constructed, respectively, to stimulate human hepatoma cell lines (HepG2 and Huh7) alone or in combination with sorafenib.The overexpression part of the experiment was divided into four groups: overexpression control group (Lv-NC), YB-1 overexpression group (Lv-YB-1), overexpression control combined with sorafenib resistance group (Lv-NC+sorafenib), YB-1 overexpression combined with sorafenib resistance group (Lv-YB-1 + sorafenib). The knockdown part of the experiment was also divided into four groups: knockdown control group (Lv-shNC), YB-1 knockdown group (Lv-shYB-1), knockdown control combined with sorafenib resistance group (Lv-shNC + sorafenib), YB-1 knockdown combined with sorafenib resistance group (Lv-shYB-1 + sorafenib). The occurrence of cell apoptosis was detected by TUNEL. The protein expression levels of phosphorylated (p)-ERK and ERK, key proteins in the extracellular regulatory protein kinase (ERK) signaling pathway, were detected by Western blot and quantified by ImageJ software. Subcutaneous tumorigenesis experiments were performed in nude mice. The effect of YB-1 on the efficacy of sorafenib was verified in vivo. The comparison between the two sets of data was carried out by an independent sample t-test. One-way ANOVA was used for comparisons between the three groups of data above. Results: Sorafenib had accelerated the occurrence of apoptosis in hepatoma cells, while YB-1 overexpression had inhibited cell apoptosis, and at the same time also inhibited the apoptosis-accelerating impact of sorafenib. On the contrary, YB-1 knockdown accelerated cell apoptosis and amplified the induction effect of sorafenib on apoptosis. Furthermore, sorafenib resistance had down-regulated p-ERK levels (HepG2: Lv-NC 0.685 ± 0.143, Lv-NC + sorafenib 0.315 ± 0.168, P < 0.05; Huh7: Lv-NC 0.576 ± 0.078, Lv-NC + sorafenib 0.150 ± 0.131, P < 0.01), whereas YB-1 overexpression had inhibited sorafenib resistance p-ERK reduction (HepG2: Lv-NC + sorafenib 0.315 ± 0.168, Lv-YB-1 + sorafenib 0.688 ± 0.042, P < 0.05; Huh7: Lv-NC + sorafenib 0.150 ± 0.131, Lv-YB-1 + sorafenib 0.553 ± 0.041, P < 0.05). YB-1 knockdown further increased sorafenib-induced p-ERK downregulation (HepG2: Lv-shNC + sorafenib 0.911 ± 0.252, Lv-shYB-1 + sorafenib 0.500 ± 0.201, P < 0.05; Huh7: Lv-shNC + sorafenib 0.577 ± 0.082, Lv-shYB-1 + sorafenib 0.350 ± 0.143, P < 0.05), which was further verified in naked mice (Lv-shNC + sorafenib 0.812 ± 0.279, Lv-shYB-1 + sorafenib 0.352 ± 0.109, P < 0.05). Conclusion: YB-1 mediates the occurrence of sorafenib resistance via the ERK signaling pathway in hepatoma cells.

MiR-133b regulates the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4 / 中南大学学报(医学版)

OBJECTIVES@#Bladder cancer is one of the most common urothelial tumors with high incidence and mortality rates. Although it has been reported that microRNA (miR)-133b can regulate tumorigenesis of bladder cancer, the mechanism remains unclear. Sex-determining region Y-box transcription factor 4 (SOX4) exhibits an important role in tumorigenesis, but it is unclear whether SOX4 and miR-133b are associated with regulation of pathogenesis of bladder cancer. This study aims to determine the expressions of SOX4 and miR-133b in bladder cancer tissues and cells, investigate their effects on the proliferation, colony formation, and invasion of bladder cancer cells, and to explore the association between miR-133b and SOX4 in regulating biological featurss of bladder cancer cells.@*METHODS@#The bladder cancer and adjacent tissue samples of 10 patients who underwent surgical resection in the Second Xiangya Hospital of Central South Universty from Januray to June 2015 were obtained. The levels of miR-133b were tested by real-time PCR, and the protein levels of SOX4 were evaluated using Western blotting in bladder cancer tissues, matched adjacent tissues, and cell lines. The correlation between miR-133b expression and SOX4 expression in bladder cancer tissues was analyzed. Using the online database TargetScan, the relationship between SOX4 and miR-133b was predicted. MiR-133b mimics, miR-133b inhibitor, and short hairpin RNA (shRNA)-SOX4 were transfected into T24 cells by Lipofectamine 2000. The relationship between miR-133b and SOX4 was also verified by a dual-luciferase reporter assay. The proliferation of T24 cells cultured for 0, 12, 48, 72, and 96 h was evaluated by cell counting kit-8 (CCK-8) assay. The colony formation capacity of bladder cancer cells was tested after 14-day culture, and cell invasion capacity was evaluated with Transwell invasion assay.@*RESULTS@#Bladder cancer tissue and bladder cancer cells had low level of miR-133b but high level of SOX4, compared with matched adjacent tissues and normal bladder epithelial cells. A negative correlation between miR-133b mRNA and SOX4 protein levels in bladder cancer tissues was also found (r=-0.84). The results of online database TargetScan showed that miR-133b targets at SOX4, and overexpression of miR-133b significantly attenuated the expression of SOX4 in T24 cells. Both overexpression of miR-133b and knockdown of SOX4 significantly inhibited the proliferation, colony formation, and invasion capacity of bladder cancer cells in vitro. SOX4 down-regulation restored the effects of miR-133b inhibitor on the proliferation, colony formation, and invasion capacity of T24 cells.@*CONCLUSIONS@#The up-regulation of SOX4 contributes to the progression of bladder cancer, and miR-133b can regulate the proliferation, colony formation, and invasion of bladder cancer cells via inhibiting SOX4.

Repair impact of vibration exercise with different frequencies on articular cartilage of rats with early knee osteoarthritis and its JNK/NF-κB, SOX9 mechanisms / 中国应用生理学杂志

Objective: To investigate the repair effect and JNK/NF-κB,SOX9 mechanisms of vibration exercise with different frequencies on articular cartilage in rats with early knee osteoarthritis. Methods: Forty-eight adult male SD rats were randomly divided into six groups(n=8):model control group(MC),high frequency vibration group 1 (GP1,60 Hz),high frequency vibration 2 group (GP2,40 Hz),medium frequency vibration group (ZP,20 Hz),minor frequency group(DP,10 Hz)and normal control group(NC). Except for NC group,the rats in each group were made into early knee osteoarthritis model after six weeks of knee joint cavity injection of papain solution and 2% mixture l-cysteine on the 1st,4 th and 7th day. Each exercise group was subjected vibration to 40 minutes a day with amplitude of 2～5 mm and 5 days a week. Four weeks later, the articular cartilage of the lateral femoral condyle of the both back leg knee joints were detected by HE staining,serine O staining and Mankin scores for morphological observation. The expression levels of JNK,NF-κB p65 and Sox9 mRNA in articular cartilage of the medial femoral condyle were detected by RT-qPCR,and the protein expressions of JNK,NF-κB p65 and Sox9 were detected by Western blot. Results: Compared with the NC group,the Mankin score in other groups was significantly higher (P＜0.01). Compared with the MC group,the Mankin score of each vibration group was significantly lower(P＜0.05),the mRNA and protein expressions of JNK and NF-κB p65 in each vibration training group were significantly lower (P＜0.01),the expressions of Sox9 mRNA and protein in vibration training group were increased significantly (P＜0.01). Compared with the higher frequency group,the Mankin score,the mRNA and protein expressions of JNK and NF-κB p65 of lower frequency group were significantly lower (P＜0.05 or P＜0.01). But the expressions of Sox9 mRNA and protein were significantly higher (P＜ 0.05 or P＜0.01). Conclusion: Vibration exercise of different frequencies may present varying degrees of cartilage repair impact in rats with early knee osteoarthritis,and the cartilage repair by low-frequency vibration training is better than that by high-frequency vibration. This can be one of the mechanisms on controlling collagen synthesis by down-regulating JNK/NF-κB expression and increasing SOX9 activity of OA articular cartilage.

Role of Y-box binding protein-1 in the development and progression of chronic liver diseases / 临床肝胆病杂志

Chronic liver diseases have various etiologies and often have poor long-term prognosis in clinical practice. Y-box binding protein-1 (YB-1) is a multifunctional protein, and in-depth studies in recent studies have found that it plays a key role in the development and progression of chronic liver diseases such as liver fibrosis and hepatocellular carcinoma (HCC). This article summarizes the role of YB-1 in chronic liver diseases such as liver fibrosis, HCC (proliferation, apoptosis, metastasis, prognosis, and drug resistance), and liver failure, so as to provide a theoretical basis for the diagnosis and treatment of chronic liver diseases.

Expression of SOX4 gene and its biological effects in endometrial carcinoma / 解剖学报

Objective To investigate the expression of sex determining region Y box protein 4(SOX4) gene and its biological effects in endometrial carcinoma. Methods 156 cases of endometrial carcinoma tissues, adjacent tissues of endometrial carcinoma and 156 cases of endometrial atypical hyperplasia were collected; Immunohistochemistry was used to detect the expression of SOX4 in endometrial cancer, endometrial dysplasia and normal endometrial tissue, and to analyze the relationship between SOX4 and the clinical characteristics of patients with endometrial cancer. After establishing the SOX4 overexpression/silencing Ishikawa cell strain using the lentivirus transfection technique, MTT, flow cytometry and Transwell chamber method were used to detect the cell proliferation, apoptosis, migration and invasion ability, and Western blotting method was used to detect SOX4, β-catenin and E-cadherin protein expression changes. Results The expression of SOX4 in endometrial cancer tissue was higher than that in normal endometrial tissue and endometrial atypical hyperplasia (P<0.05). SOX4 expression was correlated with invasion depth, International Federation of Obstetrics and Gynecoogy (FIGO) stage and lymph node metastasis (P<0.05). Compared with control group, SOX4 overexpressed Ishikawa cells have significantly increased proliferative ability, migration and invasion ability, significantly reduced apoptosis rate, significantly increased SOX4 and β-catenin protein expression, and significantly reduced E-cadherin protein expression (all P< 0.05). while the proliferation ability, migration and invasion ability of Ishikawa cells interfered by SOX4 were significantly reduced, the apoptosis rate was significantly increased, the expression of SOX4 and β-catenin protein was significantly reduced, and the expression of E-cadherin protein was significantly increased (all P<0.05). Conclusion S0X4 gene is highly expressed in endometrial cancer tissues, which may promote the development of endometrial cancer by activating Wnt/β-catenin signaling pathway.

Sex determining region Y-box 9 induced microtubule formation and epithelial⁃mesenchymal transition in human oral squamous cell carcinoma CAL27 cells / 华西口腔医学杂志

OBJECTIVES@#This study aimed to explore the effect of sex determining region Y-box 9 (SOX9) on the microtubule formation and epithelial-mesenchymal transition (EMT) of human oral squamous cell carcinoma (OSCC) CAL27 and the underlying mechanism.@*METHODS@#SOX9-shRNA1 and SOX9-shRNA2 were designed and synthesized and then transfected into CAL27 cells. The expression of SOX9 was detected by quantitative real-time polymerase chain reaction. Microtubule formation assay was used to detect the change in the number of microtubule nodules after interfering with SOX9. Immunofluorescence was used to detect the Vimentin content. Western blot was used to detect the protein expression of EMT marker molecules and Wnt/β-catenin pathway-related proteins, such as E-cadherin, N-cadherin, Fibronectin, Wnt, β-catenin, T-cell factor-4 (TCF-4).@*RESULTS@#The expression level of SOX9 significantly decreased after transfection with SOX9-shRNA1 and SOX9-shRNA2 in CAL27 cells (@*CONCLUSIONS@#Interference with SOX9 decreased Vimentin content and inhibited the microtubule formation and protein expression of EMT marker molecules, as well as the expression of proteins related to the Wnt/β-catenin pathway. Thus, SOX9 can induce microtubule formation and EMT in CAL27, which was related to the inhibition of the Wnt/β-catenin pathway activation.

Putative stemness markers octamer-binding transcription factor 4, sex-determining region Y-box 2, and NANOG in non-small cell lung carcinoma: A clinicopathological association

Background: The promising improvement in the clinical outcome of lung cancer can be possibly achieved by identification of the molecular events that underlie its pathogenesis. Cancer stem cell (CSC) being one of the subsets of tumor majorly participates in drug resistance and treatment failure because of the moderate cell cycle, lower proliferation, and increased expression of DNA repair and anti-apoptosis genes. Although many putative CSC markers exist, a precise characterization for non-small cell lung cancer is of utmost importance due to increased mortality rate and lack of targeted therapies. Hence, the article focuses on the expression of stemness-associated markers, namely octamer-binding transcription factor 4 (OCT4), NANOG, and sex-determining region Y-box 2 (SOX2) in non-small cell lung cancer (NSCLC) patients. Methods: The expression of OCT4, NANOG, and SOX2 were evaluated in 32 histopathologically confirmed NSCLC tissues using real-time polymerase chain reaction. The obtained expression was correlated with clinical and pathological manifestations using the statistical test such as Student's t-test and Pearson correlation in varied statistical software. Results: Results showed a significantly higher expression of OCT4 and NANOG compared to SOX2 in the tumor tissues. When the expression of these markers was correlated with the clinical parameters, higher expression was seen in males, patients with age above 60 years, and in adenocarcinoma subtype. In correlation with the habit, higher expression of OCT4 and SOX2 was observed in habituated patients. Expression of NANOG and OCT4 was higher even in patients with poor differentiation. Conclusion: The expression and prognostic significance of CSC markers obviously vary depending on histological NSCLC subtype. Importantly, our findings suggest that OCT4, SOX2, and NANOG network together may be promising for ongoing targeted therapies in specific NSCLC subgroups

Sex determining region Y-box 2 is a prognostic factor for head and neck squamous cell carcinoma: Evidence from 11 published investigations

Objective: The aim of this study was to review the published literature and investigate whether sex determining region Y-box 2 (SOX2) is a prognostic factor in head and neck squamous cell carcinoma (HNSCC) by conduct a meta-analysis. Materials and Methods: Trials were identified from the major electronic databases (MEDLINE, EMBASE, and Cochrane Library) using the key words “HNSCC” and “SOX2.” The overall survival (OS), disease-specific survival (DPS), and disease-free survival (DFS) were the primary outcome measures. Results: We identified 371 articles, 9 articles 11 studies with a total number of 1334 cases were eligible for inclusion of this meta-analysis. The results showed that OS (DPS) in low-expression group was higher than that in high-expression group. However, the difference between the two groups was not significant (hazard ratio [HR] = 1.30, 95% confidence interval [95% CI] = [0.88, 1.91]; P = 0.18), and there was great statistical heterogeneity (I2 = 66%, P = 0.002). After subgroup analysis, the HR for OS of the patients with reduced expression of SOX2 was 1.34 (95% CI = [1.04, 1.74], P = 0.03), and the heterogeneity became acceptable (I2 = 32%, P = 0.16). The HR for DFS of the patients with reduced expression of SOX2 was 1.39 (95% CI = [1.00, 1.93]; P = 0.05). Conclusion: The findings of this meta-analysis are indicative of that high SOX2 expression is a negative prognostic factor of HNSCC and exhibit both worse OS and DFS. However, the small sample size available for this systematic review limited the power of this quantitative meta-analysis. It may therefore be too early to place complete confidence in these results

Association of the co-expression of SOX2 and Podoplanin in the progression of oral squamous cell carcinomas - an immunohistochemical study

Abstract SOX2 is a transcription factor related to the maintenance of stem cells in a pluripotent state. Podoplanin is a type of transmembrane sialoglycoprotein, which plays an important role in tumor progression and metastasis. This study aims to determine association of SOX2 and podoplanin expression in the progression of oral squamous cell carcinomas and to elucidate the association between two proteins. Methodology: The immunohistochemical expression of SOX2 and podoplanin were evaluated in 60 cases of primary oral squamous cell carcinomas. The correlation between the SOX2 and podoplanin expression and the clinicopathological features of the tumors and the patient outcomes were assessed. Results: The expression of SOX2 was seen in 38/60 (63%) of the cases and the expression for podoplanin was seen in 45/60 (75%) cases. There was a significant inverse correlation between the expression of SOX2 and podoplanin with the tumor grade (p=0.002 and p=0.017, respectively). There was a high expression of SOX2 in 9/13 cases that presented with disease free survival. Survival analysis showed that a high expression of SOX2 correlated positively (p=0.043) with the disease-free survival. There was a significant positive association between the pattern of SOX2 and podoplanin expression (p=0.002). Conclusion: A high expression of SOX2 was associated with better disease-free survival. The expression of podoplanin was associated with the degree of differentiation of the tumors. Analysis of these biomarkers can aid in the prognosis and treatment of oral squamous cell carcinomas.

Effect of down-regulation of sex determining region Y-box 9 on epithelial mesenchymal transition and cloning of oral squamous carcinoma cells / 华西口腔医学杂志

OBJECTIVE@#To investigate the effect of sex determining region Y-box 9 (SOX9) on epithelial mesenchymal transition (EMT) and cloning of oral squamous cell carcinoma (OSCC).@*METHODS@#siRNA control, SOX9 siRNA were transfected into BcaCD885 cells in OSCC. Simultaneously, cells that did not undergo transfection were used as the control. Quantitative real time polymerase chain reaction (qRT-PCR) and Western blot were used to select SOX9 siRNA1 with enhanced interference effect. A cell cloning assay was used to determine the cell's clone formation ability. E-cadherin and Vimentin expressions were detected by immunofluorescence. The expressions of E-cadherin, matrix metalloprotease 2 (MMP-2), Vimentin and matrix metalloprotease 9 (MMP-9) were detected by Western blot. Cell invasion and migration were detected in the Transwell compartment.@*RESULTS@#The levels of SOX9 mRNA and protein in SOX9 siRNA cells were significantly lower than those of the control (P<0.05). An increase in the number of SOX9 siRNA1 cell clonesled to the considerable decrease of the number of cell invasion and migration. In addition, levels of MMP-2 and MMP-9 proteins in cells decreased significantly compared with the control (P<0.05). The level of Vimentin expression in SOX9 siRNA1 cells decreased, and expression level of E-cadherin was elevated. Cell EMT was inhibited compared with the control, and the difference was statistically significant (P<0.05).@*CONCLUSIONS@#Down-regulation of SOX9 inhibited EMT, clonogenic formation, cell invasion and OSCC migration.

The expression and significance of YB-1 in cervical squamous carcinoma / 重庆医学

Objective To detect the expression of YB-1 and to research the relationship in the occurrence and development in the cervical squamous carcinoma(SCC) tissues.Methods Immunohistochemistry(IHC) envision was used to detect the expression of chronic cervicitis,CIN Ⅰ,CIN Ⅱ-Ⅲ and SCC.The relationship of YB-1 in the clinical pathological parameters of SCC were analyzed.Results YB-1 was mainly located in the nucleus in squamous cell,sometimes in the cytoplasm.The YB-1 protein did not expression in chronic cervicitis.In CIN Ⅰ,CIN Ⅱ-lⅢ and SCC,the positive expression had a gradual increasing trend.The expression of YB-1 was satistically significant in four groups (P＜0.05).The chronic cervicitis group,CIN Ⅰ groupCIN Ⅱ-Ⅲ group compared with the SCC group restivelly,the difference was statistically significant (P＜0.05).From spearman rank correlation analysis:the expression of YB-1 was positively correlated with the degree of cervical lesions (P＜ 0.05).In the cervical squamous carcinoma group,the expression of YB-1 was not associated with clinical pathological index of SCC patients(P＞0.05).Conclusion The change of the quantity of YB-1 protein is closely related to cervical squamous cell carcinoma.

The expression of sex determining region Y-box 18 in prostate cancer and its impact on prostate cancer cell function / 中华泌尿外科杂志

Objective To explore the expression of sex determining region Y-box 18 (SOX18) in prostate cancer(PCa) and its role on prostate cancer cells.Methods The expression of SOX18 in 98 PCa tissues and 81 adjacent non-tumor tissues was detected by immunohistochemistry.The expression of SOX18 mRNA and protein in PCa cell lines were detected by q-PCR and Western blotting analysis,respectively.After knocking down SOX18 with si-RNA,the proliferation,migration and invasion of PCa cells were analyzed by CCK8,Transwell and Matrigel assays in vitro.Results The rate of high SOX18 expression in prostate cancer tissues was 73.5％ (72/98),which was higher than that in adjacent normal tissues (43.2％,35/81) (P ＜ 0.01).In addition,the rates of high SOX18 expression in clinical stage Ⅲ-Ⅳ [83.7 ％ (36/43) vs.65.5 ％ (36/55),x2 =4.131,P =0.042],pathological grading G3-4 [88.6％ (39/ 44) vs.61.7％ (33/54),x2 =9.424,P =0.002] and Gleason scores ≥ 8 [85.0％ (34/40) vs.65.0％ (38/58),x2 =4.610,P =0.032] groups were higher than those in clinical stage Ⅲ-Ⅳ,pathological grading G1-2 and Gleason scores ≤7 groups.However,there were no differences in the rate of high SOX18 expression in different age groups [77.3％ (38/54) vs.70.4％ (34/44),x2 =0.539,P =0.441].Knockdown of SOX18 notably suppressed the proliferation,migration and invasion of prostate cancer cells.Conclusions SOX18 is over-expressed in prostate cancer,and could promote the proliferation,migration and invasion ability of prostate cancer cells.

Expression of VEGF and SOX2 in squamous cell lung cancer and prognosis effect / 实用医学杂志

Objective Preliminarily discussing the effects of VEGF and SOX2 on metastasis and progno-sis of squamous cell lung carcinoma(SCLC).Methods Using immunohistochemical method to detect 47 cases of pulmonary squamous cell carcinoma and 30 cases of para-carcinoma tissue in the expression of VEGF and SOX2, using statistical methods to analyze the expression of VEGF and SOX2 and the relationship between clinical parame-ters and its relationship with prognosis. Results The positive expression rates of VEGF,SOX2 in SCLC tissues were higher than adjacent normal tissues.There was a significant correlation between VEGF and SOX2 expression. VEGF expression was associated with lymph node metastases and TNM stage.SOX2 expression was associated with tumor differentiation and lymph node status.Survival analysis indicated that VEGF(+)/SOX2(+)patients had the worst prognosis.Furthermore,multivariate analysis suggested that tumor diameter and lymph node metastases were independent prognostic factors for SCLC. Conclusion The expression of VEGF was positively correlated with lymph node metastasis and clinical stage,the expression of SOX2 was positively correlated with tumor differentia-tion degree and lymph node metastasis,and high expression of VEGF and SOX2 may indicate lung squamous can-cer patients with poor prognosis.

MiR-630 inhibits MDA-MB-231 cells migration and invasion by targeting Sox4 in triple-negative breast cancer / 重庆医学

Objective To verify whether miR-630 could inhibit MDA-MB-231 cells migration and invasion by targeting Sox4 in triple-negative breast cancer(TNBC).Methods Collection normal breast tissue and breast cancer tissue from patients undergoing breast cancer resection.RT-PCR were used to test the expression of miR-630,miR-21,miR-195,miR-134,miR-200a,miR-381 and miR-1228.Western blot were used to test the expression of COL1A1,COL1 A5,MMP-2,MMP-9 and Sox4.In vitro experiment,after miR-630 was transfected into MDA-MB-231 cells,wound healing were employed to test the migratory ability of MDA-MB-231 cells,and transwell were used to test the invasion ability of MDA-MB-231 cells.Western blot were used to investigate the expressions of COL1 Al,COL1 A5,MMP-2,MMP-9 and Sox4 in MDA-MB-231 cell.Luciferase assay was used to confirmed whether Sox43'-UTR the target gene of miR-630.Results Compared with normal breast tissue,the expression of miR-630 was decreased(P＜0.01),meanwhile the expression of COL1A1,COL1A5,MMP-2,MMP-9 and Sox4 were significantly increased in the triple-negative breast cancer tissue(P＜0.01).In the vitro experiment,compared with the control group,the expression of COL1A1,COL1A5,MMP-2,MMP-9 and Sox4 were decreased in the miR-630 group (P＜0.05);The migration activity of MDA-MB-231 cells was decreased in the miR-630 group (P＜0.01);The Luciferase activity of the Sox4-3'-UTR plasmid was significantly suppressed by miR630 (P＜0.05);Over expression of Sox4 could reverse the effect of miR-630 on MDA-MB-231(P＜0.05,P＜0.01).Conclusion In triple-negative breast cancer tissue,the expression of miR-630 decreased;miR-630 inhibits triple-negative breast cancer cells migration and invasion by targeting Sox4-3’-UTR.

Correlation Between Y-box Binding Protein-1 Expression and P-Glycoprotein in Drug-resistant Hepatocellular Carcinoma Bel-7402/ADM Cells / 医药导报

Objective To explore the correlation between Y-box binding protein-1 ( YB-1) and P-glycoprotein ( P-gp) in drug-resistant hepatocellular carcinoma ( HCC) Bel-7402/ADM cells, and speculate the related mechanism of drug resistance.Methods Bel-7402/ADM cells were developed by concentration gradient escalation and intermittent administration of large dose. The levels of YB-1 mRNA and MDR1 mRNA were detected by means of RT-PCR.Western blotting was used to detect the protein expression of YB-1 and P-gp in the Bel-7402 cells and doxorubicin resistant Bel-7402 ( Bel-7402/ADM) cells. Bel-7402/ADM cells were transfected with small interfering RNA ( siRNA) targeting human YB-1. Expression levels of YB-1 and MDR1 mRNA and protein were detected by means of RT-PCR and Western blotting. Results IC50 values of ADM on hepatoma carcinoma cells Bel-7402 and Bel-7402/ADM were (2.23±0.07) and (7.02±0.03) μmol?L-1. The mRNA expression levels of MDR1 and YB-1 were all significantly higher in Bel-7402/ADM cells than in Bel-7402 ( P<0.01) . The mRNA expression levels of MDR1 and YB-1 in Bel-7402/ADM cells transfected with YB-1 siRNA were reduced significantly (P<0.01). The protein levels of YB-1 and MDR1 in Bel-7402/ADM cells transfected with YB-1 siRNA were reduced significantly ( P<0. 05 ) . Conclusion These results suggest that the high expression level of YB-1 is probably correlated with multidrug resistance in HCC Bel-7402/ADM cells.

Correlation Between Y-box Binding Protein-1 Expression and P-Glycoprotein in Drug-resistant Hepatocellular Carcinoma Bel-7402/ADM Cells / 医药导报

Objective To explore the correlation between Y-box binding protein-1 ( YB-1) and P-glycoprotein ( P-gp) in drug-resistant hepatocellular carcinoma ( HCC) Bel-7402/ADM cells, and speculate the related mechanism of drug resistance.Methods Bel-7402/ADM cells were developed by concentration gradient escalation and intermittent administration of large dose. The levels of YB-1 mRNA and MDR1 mRNA were detected by means of RT-PCR.Western blotting was used to detect the protein expression of YB-1 and P-gp in the Bel-7402 cells and doxorubicin resistant Bel-7402 ( Bel-7402/ADM) cells. Bel-7402/ADM cells were transfected with small interfering RNA ( siRNA) targeting human YB-1. Expression levels of YB-1 and MDR1 mRNA and protein were detected by means of RT-PCR and Western blotting. Results IC50 values of ADM on hepatoma carcinoma cells Bel-7402 and Bel-7402/ADM were (2.23±0.07) and (7.02±0.03) μmol?L-1. The mRNA expression levels of MDR1 and YB-1 were all significantly higher in Bel-7402/ADM cells than in Bel-7402 ( P<0.01) . The mRNA expression levels of MDR1 and YB-1 in Bel-7402/ADM cells transfected with YB-1 siRNA were reduced significantly (P<0.01). The protein levels of YB-1 and MDR1 in Bel-7402/ADM cells transfected with YB-1 siRNA were reduced significantly ( P<0. 05 ) . Conclusion These results suggest that the high expression level of YB-1 is probably correlated with multidrug resistance in HCC Bel-7402/ADM cells.

The expression and clinical significance of stem cell transcription factor SOX2, OCT4 in gastric ;cancer tissues varying degrees of cell differentiation / 中国癌症杂志

Background and purpose:Differentiation of tumor tissue is an important factor on determining the prognosis of gastric cancer. This study aimed to investigate the expression levels and clinical signiifcance of gender determining region Y-box 2 (SOX2) gene and octamer binding factor 4 (OCT4) gene in gastric cancer tissues varying different differentiation degrees. Methods: Sixty cases with gastric cancer were recruited in this study. The gastric cancer tissues and corresponding normal mucosa of the 60 cases were obtained. The mRNA and protein level of SOX2, OCT4 gene are evaluated by the quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry, respectively. The relationship between the expression levels of SOX2, OCT4 gene and clinical pathological parameters were also analyzed in this study. Results:The expression of SOX2 in both mRNA and protein levels had no signiifcant difference between the well-differentiated gastric cancer tissues and normal gastric mucosa (mRNA levels:t=0.1033, P>0.05;protein levels:t=0.116, P>0.05). However, both the mRNA and protein expression of SOX2 in patients with well-differentiated gastric cancer tissues were signiifcant higher than not only in patients with moderately differentiated gastric carcinoma (mRNA levels: t=12.48, P0.05;protein levels:t=1.064, P>0.05). Immunohistochemical study demonstrated that the positive rate of SOX2 in patients with well-differentiated gastric cancer tissues (10/21) were higher than in patients with not only moderately differentiated gastric carcinoma (7/20) but also poorly differentiated gastric carcinoma (2/19, P0.05). Nevertheless, the expression of SOX2, OCT4 were positive or negative correlated with the pathological staging, the degree of inifltration and lymph node metastasis (P<0.05). Conclusion:Decreased SOX2 expression and increased expression level of OCT4 can promote the formation, development and invasion of gastric cancer and they may become biomarkers or the diagnosis, treatment and prognosis evaluation in gastric carcinoma.

Correlation of YB-1 up-regulation and epithelial-mesenchymal transition during tumorigenesis and pro-gression of cervical carcinoma / 国际肿瘤学杂志

Objective To investigate the clinicopathologic significance of Y-box binding protein-1 (YB-1)expression in cervical cancer and its correlation with epithelial-mesenchymal transition. Methods A series of 202 samples,including 50 cases of normal cervical tissues,100 cases of cervical intraepithelial neo-plasia(CIN)and 52 cases of squamous cell carcinoma(SCC),were examined YB-1 and E-cadherin by immu-nohistochemical staining. Results The E-cadherin cell membrane immunoreactivity for normal/ CINⅠ,CINⅡ-Ⅲ,and SCC tissues were 100% ,64% and 3. 85% ,respectively( χ2 = 40. 909;χ2 = 119. 088;χ2 =25. 274;P < 0. 05). The negative and aberrant expression of E-cadherin was higher in metastatic SCC (100. 0% ,20 / 20)than that in non-metastatic SCC(68. 75% ,22 / 32)(χ2 = 5. 857,P = 0. 016). 94. 23%(49 / 52)cases of SCC exhibited strong YB-1 cytoplasmic immunoreactivity. The positive rates in normal/ CINⅠand CINⅡ-Ⅲ were 0(0 / 100)and 10. 00%(5 / 50)(χ2 = 72. 591;χ2 = 139. 059;χ2 = 5. 857;P < 0. 05). The cytoplasmic expression of YB-1 was higher in metastatic SCC(100. 0% ,20 / 20)than that in non-metastatic SCC(59. 38% ,19 / 32)(χ2 = 10. 833,P = 0. 001). The rates were 60. 71%(17 / 28)and 91. 67%(22 /24)in early stage SCC and late stage SCC(χ2 = 6. 603,P = 0. 01). Conclusion YB-1 over-expression is as-sociated with the malignant transformation of cervical epithelium,stage progression and metastasis of cervical cancer. The up-regulation of YB-1 is also associated with the down-regulation of E-cadherin,and it may predict the malignant transformation of CIN and distal metastasis of cervical cancer.

A Korean boy with 46,XX testicular disorder of sex development caused by SOX9 duplication

The 46,XX testicular disorder of sex development (DSD), also known as 46,XX male syndrome, is a rare form of DSD and clinical phenotype shows complete sex reversal from female to male. The sex-determining region Y (SRY) gene can be identified in most 46,XX testicular DSD patients; however, approximately 20% of patients with 46,XX testicular DSD are SRY-negative. The SRY-box 9 (SOX9) gene has several important functions during testis development and differentiation in males, and overexpression of SOX9 leads to the male development of 46,XX gonads in the absence of SRY. In addition, SOX9 duplication has been found to be a rare cause of 46,XX testicular DSD in humans. Here, we report a 4.2-year-old SRY-negative 46,XX boy with complete sex reversal caused by SOX9 duplication for the first time in Korea. He showed normal external and internal male genitalia except for small testes. Fluorescence in situ hybridization and polymerase chain reaction (PCR) analyses failed to detect the presence of SRY, and SOX9 intragenic mutation was not identified by direct sequencing analysis. Therefore, we performed real-time PCR analyses with specific primer pairs, and duplication of the SOX9 gene was revealed. Although SRY-negative 46,XX testicular DSD is a rare condition, an effort to make an accurate diagnosis is important for the provision of proper genetic counseling and for guiding patients in their long-term management.

Expression of Y-box-binding protein-1 and epithelial-mesenchymal transition markers in colorectal cancer / 国际肿瘤学杂志

Objective To detect the expressions of Y-box-binding protein-1(YB-1)and epithelial-mesenchymal transition(EMT)markers(E-cadherin and N-cadherin)in colorectal cancer(CRC),to analyze the relationship between the expression of YB-1 and clinicopathological parameters,to evaluate the correlations among YB-1,E-cadherin and N-cadherin. Methods The expressions of YB-1,E-cadherin and N-cadherin in 120 primary CRC tumors and corresponding normal tissues were detected by western blot and immunohistochem-istry and the results were analyzed. Results The expressions of YB-1,E-cadherin and N-cadherin in tumors were significantly different from those in corresponding normal tissues(χ2 = 47. 373,P ﹤ 0. 05;χ2 = 83. 145, P ﹤ 0. 05;χ2 = 41. 832,P ﹤ 0. 05). The expression of YB-1 in tumors was associated significantly with tumor differentiation,tumor invasion,lymph node metastasis and distance metastasis(χ2 = 8. 077,P = 0. 008;χ2 =8. 178,P = 0. 006;χ2 = 15. 152,P ﹤ 0. 001;χ2 = 7. 368,P = 0. 011). It was negatively correlated with E-cadherin expression(r = - 0. 238,P = 0. 009),but positively correlated with N-cadherin expression(r =0. 361,P ﹤ 0. 001). Conclusion YB-1 may promote the occurrence and development of CRC by participating in EMT program.