Research progress of Sox2 gene in eye diseases / 国际眼科杂志(Guoji Yanke Zazhi)

@#Sox2 gene is a member of sex determination region of Y chromosome(SRY)related gene family, and it is one of the key transcription factors to maintain the pluripotency and self-renewal characteristics of embryonic stem cells. Sox2 participates in a variety of biological processes, such as regulating cell proliferation and apoptosis, and participating in the formation and development of tumors. However, the review literature on the role of Sox2 gene in eye diseases has not been reported. This article reviews the expression level of Sox2 gene, related signal pathways and clinical application potential, so that readers can understand more comprehensive the role of Sox2 gene in eye diseases, and to carry out more in-depth research.

Study on the effects and mechanism of Linc01278 on the biological behavior of prostate cancer cells / 中华内分泌外科杂志

Objective:To investigate the effect and molecular mechanism of long non-coding RNA (Linc01278) on the proliferation, invasion and migration, and tumor phenotype of prostate cancer cells.Methods:Prostate cancer tissues and corresponding normal tissues adjacent to the cancer were obtained in 46 patients with prostate cancer confirmed by the hospital from Dec. 2018 to Dec. 2019. Real-time fluorescence quantitative PCR (qPCR) was used to detect the expression levels of Linc01278 and miR-145 in prostate cancer tissues and adjacent normal tissues. The prostate cancer PC-3 cells were transfected with plasmids and cells were divided into four groups: blank group, control group, overexpression group and rescue group. The blank group was not given any treatment; the control group was transfected with blank control vector and miRNA Control; the overexpression group was transfected with Linc01278 overexpression vector and miRNA Control; the rescue group was transfected with Linc01278 overexpression vector and miR-145 mimics. Bioinformatics analysis was used to predict the binding site of Linc01278 to miR-145. Dual Luciferase Reporter Gene Assay was used to analyze the adsorption of Linc01278 on miR-145; Transwell experiment was used to detect the invasion and migration ability of the four groups of cells; CCK-8 method was used to detect the cell proliferation ability of the four groups of cells. Western blot was used to detect the expression of OCT4 and SOX2 in the four groups of cells; qPCR was used to detect the expression of OCT4, SOX2 and miR-145 in the four groups of cells.Results:Compared with adjacent normal tissues, Linc01278 was significantly higher in prostate cancer tissues (adjacent normal tissues: 0.012±0.002 vs prostate cancer tissues: 0.022±0.002, P=0.0072) , while miR-145 was significantly lower (adjacent normal tissues: 0.117±0.011 vs prostate cancer tissues: 0.081±0.007, P=0.0005) . Correlation of both was negative significantly ( P=0.0012) . Targetscan analysis revealed that the 804-825 position of the Linc01278 transcript had a complementary base pairing with miR-145. The results of the double luciferase reporter gene showed that miR-145 mimics could significantly reduce the luciferase activity of Linc01278 ( P<0.01) . Compared with the blank group and the control group, the invasion and migration cells, the relative proliferation ability, the expression of Oct4 and Sox2 mRNA and protein were significantly increased, and the expression of miR-145 was significantly decreased in the overexpression group ( P<0.05) . While compared with the overexpression group, the invasion and migration cells, the relative proliferation ability, Oct4 and Sox2 were significantly decreased in the rescue group, and the expression of miR-145 was significantly increased ( P<0.01) . Conclusion:Linc01278 may promote the proliferation, invasion and migration of prostate cancer cells by specifically adsorbing miR-145.

Elevated expression of stemness genes in adipose-derived mesenchymal stem cells cultured on fibrin scaffold

In regenerative medicine, MSCs need to be pluripotent for better results. In this study, the effect of fibrinscaffold on expression of stemness genes was examined. Adipose-derived MSCs were cultured in tissue cultureplates (2D) and 3-dimensional (3D) fibrin scaffolds. The effect of fibrin scaffold on proliferation of adiposederived MSCs was evaluated by MTT assay. The expression of stemness genes (OCT4 and SOX2) wereevaluated by qRT-PCR, and flow cytometry was done for Nanog protein level. Cultured MSCs on fibrinscaffold were able to proliferate according to data obtained by MTT assay. Expression of OCT4 and SOX2 hada significant increase in cells were cultured in 3D condition compared to 2D condition (P \0.05). Also,increased expression of Nanog protein in 3D culture was observed (P \0.05). OCT4 and SOX2 in 3Dcondition increased two-fold and three-fold respectively in 2D and 3D conditions. Moreover, expression ofNanog increased 30% more than in 2D condition. Evaluation of important pluripotency regulators such asOCT4, SOX2, and Nanog showed that fibrin scaffolds are useful instruments to maintain stemness of MSCs,which is essential in field of stem cell therapy and regenerative medicine.

Newborn transient patterned hyperpigmentation and anophthalmia / Patrón de hiperpigmentación transitoria del recién nacido y anoftalmia

Abstract Background: Transient pigmentary lines of the newborn are uncommon cutaneous lesions of unknown etiology. To date, only a few cases have been described. Case report: A patient with a combination of transient pigmentary lines and ocular malformation is described. Molecular analysis of the SRY-box 2 (SOX2) and MIFT genes was conducted to rule out any monogenetic etiology. Conclusions: Worldwide, this is the eighth case of transient pigmentary lines of the newborn reported, and the first associated with anophthalmia. No mutations in the analyzed genes (SOX2 and MIFT) were identified. Therefore, somatic mutations could be responsible for this anomaly.

Resumen Introducción: Las líneas transitorias pigmentarias del recién nacido son lesiones cutáneas poco comunes. A la fecha, pocos casos se han descrito. Caso clínico: Paciente neonato con la combinación de líneas transitorias hiperpigmentadas y una malformación ocular. Se realizó secuenciación molecular de los genes SOX2 y MIFT para descartar una etiología monogénica. Conclusiones: En todo el mundo, este es el octavo caso reportado de líneas transitorias hiperpigmentadas del recién nacido, y el primero asociado con anoftalmia. No se identificaron mutaciones en los genes estudiados (SOX2 y MIFT). Por lo tanto, las mutaciones somáticas pueden ser la causa de la afección.

Cd20 expression down-regulated by SOX2 induces rituximab resistance in diffuse large b-cell lymphoma / 肿瘤

Objective: To explore the molecular mechanism of resistance to rituximab in diffuse large B-cell lymphoma (DLBCL) during treatment with R-CHOP (rituximab+cyclophosphamide+ doxorubicin+vincristine+prednisone). Methods: FCM was used to detect the expression level of CD20 and the three membrane complement regulatory proteins CD46, CD55 and CD59 in parental cells LY8 [germinal center B-cell-like (GCB) subtype] and NU-DUL-1 [activated B-cell-like (ABC) subtype], rituximab (R) resistance cells LY8-R and NU-DUL-1-R, chemotherapy drug cyclophosphamide+doxorubicin+ vincristine (CHO) resistance cells LY8-CHO and NU-DUL-1-CHO, and rituximab combined with CHO resistance (RCHO) LY8-RCHO and NU-DUL-1-RCHO cells. The expression level of CD20 protein and mRNA were detected by Western blotting and real-time fluorescent quantitative PCR, respectively. The expression levels of CD20, CD46, CD55 and CD59 in SRY (sex determining region Y)-box 2 (SOX2) overexpression of parental LY8 and NU-DUL-1 cells as well as SOX2 gene silencing of LY8-RCHO and NU-DUL-1-RCHO cells were detected by FCM method. Furthermore, in tumor tissues of clinical 25 DLBCL patients with at least 6 circles of R-CHOP regimen treatment, immunohistochemical were used to detect the expression levels of CD20 and SOX2 before and after the treatment. Results: Compared with the parental cells, in the LY8-R, LY8-RCHO and NU-DUL-1-R and NU-DUL-1-RCHO cells that developed rituximab resistance, not in LY8-CHO and NU-DUL-1-CHO cells which resistant to chemotherapy, the expression level of CD20 was significantly reduced (all P < 0.001), while the expression levels of CD46, CD55 and CD59 were also decreased (all P < 0.05). The expression level of CD20 protein and mRNA were significantly reduced (P < 0.001and P < 0.01). Furthermore, in the parental LY8 and NU-DUL-1 cells, overexpression of SOX2 significantly reduced the expression level of CD20 (P < 0.000 1), while knockdown of SOX2 in LY8-RCHO and NU-DUL-1-RCHO cells significantly increased the expression level of CD20 (P < 0.0001). It was further found that the expression level of CD20 in tumor tissues of DLBCL patients was significantly decreased after R-CHOP treatments (P < 0.01), and the expression level of SOX2 was significantly increased (P < 0.001). After comprehensive analysis, it was found that there was a negative correlation between CD20 and SOX2 expression in tumor tissues (P < 0.000 1). Conclusion: SOX2 induces DLBCL resistance to rituximab by reducing the expression level of CD20.

miR-135a knockdown inhibits the malignant biological behaviors and promotes oxaliplatin-sensitivity of human laryngeal carcinoma Hep-2 cells by down-regulation of SOX2 / 中国肿瘤生物治疗杂志

@# Objective: To investigate the effect of miR-135a on the malignant biological behaviors of human laryngeal carcinoma epithelial Hep-2 cells and its sensitivity to oxaliplatin. Methods: Samples of laryngeal carcinoma tissues and para-cancerous tissues were collected from 10 patients who underwent laryngectomy in Nanyang Hospital Affiliated to Zhengzhou University-Nanyang City Center Hospital from January 2018 to June 2018. The expression of miR-135a in laryngeal carcinoma tissues and Hep-2 cells was detected by qPCR.After being transfected with miR-135 inhibitor, cell proliferation viability of Hep-2 cells was measured by CCK-8 assay, cell colony formation ability was detected by colony formation assay, and cell proliferation invasion and migration abilities were detected by Transwell analysis, and the expression of SOX2 protein in Hep-2 cells was detected by WB. Hep-2 cells transfected with miR-135 inhibitor were further treated with various concentrations (0.5, 1.0, 1.5 and 2.0 μmol/L) of oxaliplatin, and the cell proliferation viability was detected by CCK-8 while cell apoptosis was detected by Annexin-V-FITC/PI double staining flow cytometry. miR-135a inhibitor plasmid, control pcDNA empty vector (SOX2-Con) plasmid, and pcDNA-SOX2 (SOX2-OE) plasmid were transfected into Hep-2 cells to construct the miR-135a inhibitor+SOX2-Con group and miR-135a inhibitor+SOX2-OE group, and the cell viability, cell colony formation ability, cell invasion and migration ability in two groups were detected. Results: Compared with para-cancerous tissues, miR135a expression in laryngeal cancer tissues was significantly increased (P<0.01). Compared with normal NHP cells, miR-135a expression in Hep-2 cells was significantly increased (P<0.01). miR-135a inhibitor significantly reduced the expression level of miR-135a in Hep-2 cells (P<0.01). miR-135a knockdown significantly reduced the cell proliferation viability, cell colony number, migration, invasion and SOX2 expression in Hep-2 cells (all P <0.01), but significantly enhanced the sensitivity of Hep-2 cells to oxaliplatin (P<0.01). Compared with miR-135a inhibitor+SOX2-Con group, the cell proliferation viability, cell colony number, migration and invasion of Hep-2 cells in miR-135a inhibitor+SOX2-OE group were significantly increased (P<0.01); Meanwhile, the cells of the 2 groups were treated with different concentrations of oxaliplatin, and the results of CCK-8 assay showed that, compared with the miR-135a inhibitor+ SOX2-Con group, the cell proliferation viability of Hep-2 cells in miR-135a inhibitor+SOX2-OE group was significantly increased (P< 0.01). Conclusion: miR-135a knockdown inhibits the malignant biological behaviors and promotes oxaliplatin-sensitivity of Hep-2 cells possibly by inhibiting the expression of the transcription factor SOX2.

Mutations in foregut SOX2 cells induce efficient proliferation via CXCR2 pathway

Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2 foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as Kras and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2 cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and Kras expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics.

Regeneration of Neural Networks in Immature Teeth with Non-Vital Pulp Following a Novel Regenerative Procedure

BACKGROUND AND OBJECTIVES: Recombinant amelogenin protein (RAP) was reported to induce soft-tissue regeneration in canine infected endodontically treated permanent teeth with open apices. To characterize identities of the cells found in the RAP regenerated tissues compared to authentic pulp by identifying: 1) stem cells by their expression of Sox2; 2) nerve fibers by distribution of the axonal marker peripherin; 3) axons by their expression of calcitonin gene–related peptide (CGRP); 4) the presence of astrocytes expressing glial fibrillary acidic proteins (GFAP).METHODS: A total of 240 open-apex root canals in dogs were used. After establishment of oral contamination to the pulp, the canals were cleaned, irrigated, and 120 canals filled with RAP, and the other 120 with calcium hydroxide.RESULTS: After 1, 3, and 6 months, teeth were recovered for immune-detection of protein markers associated with native pulp tissues. Regenerated pulp and apical papilla of RAP group revealed an abundance of stem cells showing intense immunoreactivity to Sox2 antibody, immunoreactivity of peripherin mainly in the A-fibers of the odontoblast layer and immunoreactivity to CGRP fibers in the central pulp region indicative of C-fibres. GFAP immunoreactivity was observed near the odontoblastic, cell-rich regions and throughout the regenerated pulp.CONCLUSIONS: RAP induces pulp regeneration following regenerative endodontic procedures with cells identity by gene expression demonstrating a distribution pattern similar to the authentic pulp innervation. A- and C-fibers, as well as GFAP specific to astrocytic differentiation, are recognized. The origin of the regenerated neural networks may be derived from the Sox2 identified stem cells within the apical papilla.

The expression and function of miR-450b-5p in hepatocellular carcinoma / 西安交通大学学报(医学版)

Objective: To investigate the expression, clinical significance and biological function of miR-450b-5p in hepatocellular carcinoma (HCC) so as to make a preliminary exploration of the mechanism in HCC. Methods: Real-time PCR was used to detect miR-450b-5p expression in HCC tissues and cells. Statistical analysis was employed to explore the correlations of miR-450b-5p with clinicopathologic features and prognosis. And Cox regression analysis was applied to analyze the relationship between clinicopathologic characteristics and prognosis. Transwell assay and MTT assay were used to study the effects of miR-450b-5p on migration, invasion and proliferation of HCC cells. Bioinformatics tools were applied to predict the potential target gene of miR-450b-5p. Luciferase reporter assay and Western blot were employed to determine the correlation between miR-450b-5p and its target gene. Results: miR-450b-5p was significantly down-regulated in HCC tissues and cell lines (P<0.001). miR-450b-5p expression was significantly correlated with tumor size (P=0.026), portal vein infiltration (P=0.013), TNM stage (P=0.020), and the prognosis of HCC patients. Cox regression analysis showed that miR-513a-5p expression was an independent prognostic factor for the HCC patients' survival. Overexpressed miR-450b-5p notably inhibited migration, invasion and proliferation of MHCC-97H cells, while miR-450b-5p inhibitors had the opposite effects on Hep3B cells. Bioinformatics analysis suggested that Sex Determining Region Y Box 2 (SOX2) might be the target of miR-450b-5p. Furthermore, luciferase reporter assay indicated that the luciferase activity of SOX2-3'-UTR was negatively regulated by miR-450b-5p. Consistently, Western blot showed that miR-450b-5p negatively regulated the expression of SOX2 in HCC cells. Conclusion: miR-450b-5p suppresses migration, invasion and proliferation of HCC cells by targeting SOX2.

Effect of miR-126 on proliferation and apoptosis in colon cancer cells via targeting regulation of SOX2 expression / 中国比较医学杂志

Objective To explore the effect of miR-126 on proliferation and apoptosis in colon cancer cells via targeting regulation of SOX2 expression. Methods miR-126 mimics and miR-126 NC were transfected into SW480 cells by liposome LipofectamineTM2000. The expression of miR-126 was detected by RT-PCR. Cell viability was determined by MTT staining. Cell apoptosis and cell cycle were detected by flow cytometry. The expression of SOX2 protein and mRNA was measured by western blot and RT-PCR. Luciferase reporter analysis was performed. Results Compared with miR-126 NC, the expression of miR-126 was upregulated(P< 0.01),cell viability was reduced(P< 0.01),early cell apoptosis rate and late apoptosis rate were increased(P< 0.01), cell cycle was arrested at G1 phase(P< 0.01), meanwhile, miR-126 mimics targeted downregulation of the expression of SOX2 protein and mRNA(P< 0.01). Conclusions miR-126 mimics can inhibit SW480 cell proliferation and induce cell apoptosis by targeting downregulation of expression of SOX2.

Inhibitory effect of metformin on aldehyde dehydrogenase positive gastric cancer stem cells and its mechanism / 解放军医学杂志

Objective To investigate the inhibitory effect of metformin (Met) on ALDH positive (ALDH+) gastric cancer stem cells and its mechanism.Methods ALDH+ and ALDH cells were isolated from human gastric cancer cell line MKN45 by flow cytometry.The characteristics of cancer stem cells of ALDH+ cells was verified by self-renewing ability,differentiation capacity experiments and tumorigenicity in nude mice.1mmol/L Met group,5mmol/L Met group and control group (MKN45 cell) were set up.After being acted on MKN45 cell for 48h,the proportion ofALDH+ cells in each group was detected by flow cytometry.RT-PCR test was performed to detect the expression of Oct4,Sox2 and AKT genes in the 3 groups.Results The cell identification showed that the self-renewal ability,differentiation capacity and tumorigenicity of ALDH+ cells were higher than that of ALDH-cells.Drug experiments indicated that the proportion ofALDH+ cells in control group,lmmol/L Met group and 5mmol/L Met group were 36.5％ ± 5.4％,15.6％ ± 1.9％ and 7.6％ ± 1.6％,respectively.The difference between the 3 groups was statistically significant (P＜0.01).RT-PCR revealed that the expressions of Sox2 and AKT genes decreased after Met treatment,and decreased with the increase of Met concentration.The expression of Oct4 gene was higher in 1 mmol/L Met group than in control group,and was lower in 5mmol/L Met group than in control group.Conclusion Met may inhibit the growth ofALDH+ gastric cancer stem cells and the expression ofAKT gene,and can be used as a target drug for the clinical treatment of gastric cancer.

Correlation of Cancer Stem-Cell Markers OCT4, SOX2, and NANOG with Clinicopathological Features and Prognosis in Operative Patients with Rectal Cancer

PURPOSE: To investigate the association of cancer stem-cell markers [octamer-binding transcription factor 4 (OCT4), sex determining region Y-box 2 (SOX2), and Nanog homebox (NANOG)] expression with clinicopathological properties and overall survival (OS) in operative rectal cancer (RC) patients receiving adjuvant therapy. MATERIALS AND METHODS: 153 patients with primary RC receiving surgery were enrolled. Tumor tissue and paired adjacent normal tissue sample were collected, and OCT4, SOX2, and NANOG expressions were assessed by immunofluorescent staining. The median follow-up duration was 5.2 years, and the last follow-up date was August 2016. RESULTS: Tumor tissue OCT4 (p < 0.001), SOX2 (p=0.003), and NANOG (p < 0.001) expressions were higher than those in adjacent tissue. OCT4 expression was positively correlated with pathological grade (R=0.185, p=0.022), tumor size (R=0.224, p=0.005), and N stage (R=0.170, p=0.036). NANOG expression was positively associated with tumor size (R=0.169, p=0.036). Kaplan-Meier suggested that OCT4+ was associated with worse OS compared with OCT4− (p < 0.001), while no association of SOX2 (p=0.121) and NANOG expressions (p=0.195) with OS was uncovered. Compared with one or no positive marker, at least two positive markers were associated with shorter OS (p < 0.001), while all three positive markers were correlated with worse OS compared with two or less positive markers (p < 0.001). Multivariate Cox's analysis revealed that OCT4+ (p < 0.001) and N stage (p=0.046) were independent factors for shorter OS. CONCLUSION: Tumor tissue OCT4 expression was correlated with poor differentiation, tumor size, and N stage, and it can serve as an independent prognostic biomarker in operative patients with RC receiving adjuvant therapy.

Estudo da expressão imunohistoquímica de SO2, FGF-10 e WNT-1 em lesões odontogênicas epiteliais benignas / Study of the immunohistochemical expression of SO2, FGF-10 and WNT-1 in benign epithelial odontogenic lesions

Os dentes desenvolvem-se a partir de interações sequenciais entre o epitélio e o mesênquima derivado da crista neural em diferentes estágios de histodiferenciação e morfodiferenciação. Ao final da odontogênese, espera-se que as estruturas que participaram da formação destes tecidos desapareçam ou permaneçam quiescentes. Não é incomum que os remanescentes epiteliais da odontogênese originem lesões, como cistos e tumores odontogênicos. No desenvolvimento dentário precoce, a manutenção das células-tronco é regulada por uma série de fatores de transcrição específicos, que inclui OCT-4, SOX-2, Nanog, Stat-3 e c-Myc e diversos outros genes Homeobox e vias de transcrição (SHH, Wnt/ß-catenina, FGF, BMP) contribuem para o destino e diferenciação celular. No entanto, há a participação destes genes e vias na patogênese de vários tipos de tumores. O objetivo do presente estudo foi avaliar a imunoexpressão de SOX2, FGF-10 e Wnt-1 em uma série de casos de lesões odontogênicas e alguns espécimes de germes dentários. A amostra consistiu de 20 Ceratocistos Odontogênicos (CO), 20 Ameloblastomas sólidos (AM), 20 Tumores odontogênicos adenomatoides (TOA), 10 Tumores odontogênico epitelial calcificante (TOEC) e 05 casos de germes dentários usados comparativamente. A imunoexpressão foi avaliada de acordo com o percentual de células epiteliais imunomarcadas e intensidade de células positivas resultando na pontuação de imunomarcação total (PIT) que variou de 0 a 7. A análise da imunoexpressão da SOX2 revelou positividade na maioria dos casos das lesões estudadas. A pontuação de imunomarcação para SOX2 revelou haver diferença estatisticamente significativa entre os grupos de lesões estudadas, com maior frequência em CO e TOEC (p <0,001). Após o pareamento, observou-se diferença significativa entre AM e CO, AM e TOEC, CO e TOA, CO e TOEC e, TOA e TOEC (p <0,05). A análise da imunoexpressão da FGF-10 e Wnt-1 revelou positividade em todos os casos das lesões estudadas, mas sem diferença estatisticamente significativa entre os grupos de lesões estudadas (p = 0,628). Houve diferença significativa em relação aos escores de positividade para Wnt-1 (p <0,001) com maior frequência em CO e TOA. Após o pareamento, observou-se existir diferença estatisticamente significativa entre AM e CO, AM e TOEC, CO e TOEC e, TOA e TOEC (p <0,05). O padrão de expressão de SOX2, FGF-10 e Wnt-1, em germes dentários e nas lesões odontogênicas aqui avaliadas, confirma a participação destas vias na odontogênese e também no desenvolvimento das lesões odontogênicas (AU).

Dental development occurs from sequential interactions between the epithelium and the mesenchyme derived from the neural crest at different stages of histodifferentiation and morphodifferentiation. At the end of tooth development, the structures that participated in the formation of these tissues are expected to disappear or remain quiescent. It is not uncommon that the epithelial remnants of the tooth development originate lesions such as odontogenic cysts and tumors. In early tooth development, stem cell maintenance is regulated by specific transcription factors, which includes OCT-4, SOX-2, Nanog, Stat-3 and c-Myc and several other Homeobox genes and transcription pathways (SHH, Wnt/ß-catenin, FGF, BMP) contribute to cell fate and differentiation. However, there is involvement of these genes and pathways in the pathogenesis of several types of tumors. The aim of the present study was to evaluate the immunoexpression of SOX2, FGF-10 and Wnt-1 in a case series of odontogenic lesions and some specimens of dental germs. The sample consisted of 20 Odontogenic Keratocysts (OK), 20 solid ameloblastomas (AM), 20 adenomatoid odontogenic tumors (AOT), 10 calcifying epithelial odontogenic tumors (CEOT) and 5 dental gerns for comparison. Immunoexpression was evaluated according to the percentage of immunostained epithelial cells and intensity of the positive cells resulting in total immunostaining score (PIT) ranging from 0 to 7. The analysis of SOX2 immunoexpression revealed positivity in most cases of the lesions studied. The immunostaining score for SOX2 revealed a statistically significant difference between the groups of lesions studied, with a higher frequency in OK and CEOT (p < 0.001). After pairing, we observed a significant difference between AM and OK, AM and CEOT, OK and AOT, OK and CEOT, and AOT and CEOT (p <0.05). Analysis of the FGF-10 and Wnt-1 immunoexpression revealed positivity in all cases of the lesions studied, with no statistically significant difference between the groups of lesions studied (p = 0.628). There was a significant difference in relation to the positivity scores for Wnt-1 (p <0.001) with higher frequency in OK and AOT. After pairing, there was a statistically significant difference between AM and OK, AM and CEOT, OK and CEOT and, AOT and CEOT (p <0.05). The expression pattern of SOX2, FGF-10 and Wnt-1 in dental germs and odontogenic lesions evaluated here confirms the participation of these pathways in the tooth development as well as in the development of odontogenic lesions (AU).

miR-429 Negatively Regulates Osteosarcoma Stem Cell-like Properties by Targeting Sox2 / 中国医科大学学报

Objective To investigate the role of miR-429 in osteosarcoma stem cells.Methods We employed different approaches to test the expression of miR-429 in osteosarcoma stem cells.miR-429-high and miR-429-low cells were separated using molecular probes and their stem cell-like properties were compared.The effect of miR-429 on osteosarcoma stem cell-like properties was further tested through transfection assays.Furthermore,the miR-429 downstream target gene was confirmed by luciferase assay.Results The expression of miR-429 in osteosarcoma stem cells was much lower than that in control cells.miR-429-high cells displayed fewer stem celllike properties than did miR-429-low cells.These observations were confirmed by transfection assays.Additionally,our luciferase assays showed that miR-429 regulates Sox2 at the post-transcriptional level.Conclusion miR-429 negatively regulates osteosarcoma stem celllike properties by targeting Sox2.

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.

Expressions and roles of SOX families in glioma / 国际肿瘤学杂志

Glioma is a common malignant tumor of nervous system.Many genes of SOX family are closely related to the genesis and development of glioma,among which SOX2,SOX4,SOX7,SOX9 gene are all abnormal in glioma.SOX2 gene is highly expressed in glioma and has positive correlation with the malignant grade of glioma.SOX2 gene coordinates with many factors and promotes the genesis and development of glioma.SOX4 gene plays as both a oncogene and a tumor suppressor gene in brain glioma,and can regulate a variety of factors.SOX7,as a tumor suppressor gene,shows low expression in glioma,and suppresses the genesis of brain glioma by regulating the related factors and signaling pathways.SOX9 gene is highly expressed in glioma tissues,and promotes tumorigenesis and metastasis of glioma by coordinating with a variety of factors,and can be used as an important risk factor for the prognosis of glioma patients.

Expressions and roles of SOX families in glioma / 国际肿瘤学杂志

Glioma is a common malignant tumor of nervous system.Many genes of SOX family are closely related to the genesis and development of glioma,among which SOX2,SOX4,SOX7,SOX9 gene are all abnormal in glioma.SOX2 gene is highly expressed in glioma and has positive correlation with the malignant grade of glioma.SOX2 gene coordinates with many factors and promotes the genesis and development of glioma.SOX4 gene plays as both a oncogene and a tumor suppressor gene in brain glioma,and can regulate a variety of factors.SOX7,as a tumor suppressor gene,shows low expression in glioma,and suppresses the genesis of brain glioma by regulating the related factors and signaling pathways.SOX9 gene is highly expressed in glioma tissues,and promotes tumorigenesis and metastasis of glioma by coordinating with a variety of factors,and can be used as an important risk factor for the prognosis of glioma patients.

Study on anti-tumor mechanism of sinomenine / 中国免疫学杂志

Objective:To investigate the anti-proliferation and anti-metastasis effects and study the molecular mechanism of sinomenine in cell line(HepG2).Methods: HepG2 cells were cultured together with different treatment concentrations of sinomen-ine.The effect of sinomenine on inhibition of growth of HepG2 cells were determined by methyl thiazolyl tetrazolium(MTT) assay.The effect of sinomenine on inhibiting metastasis of HepG2 cells were determined by Transwell assay.The inhibitory effect of sinomenine on reverse transcriptase(RT) was studied using inhibitory kinetic method,on the basis,the reactive oxygen species(ROS) of HepG2 cells was monitored by indirect fluorescent labeling.The protein expressions of CASP3,CASP9,CAV1 and SOX2 were analyzed by Western blot experiment.Results: Sinomenine inhibited the proliferation and metastasis of HepG2 cells significantly.Sinomenine had a good inhibitory effect on the growth of HepG2 cells,half inhibitory concentration(IC50) was (15.35±2.43)μmol/L.Sinomenine was RT inhibitor,IC50 was (21.32±2.43)μmol/L.The Western blot showed that CASP3,CASP9 and CAV1 were up-regulated and SOX2 was down-regulated by the sinomenine treatment in HepG2 cells.Conclusion: The potential molecular mechanism of sinomenine suppresses proliferation and metastasis of HepG2 cells by up-regulation of CASP3,CASP9,CAV1 and down-regulation of SOX2.

Prognostic value of Sox2 expression in digestive tract cancers: A meta-analysis / 华中科技大学学报（医学）（英德文版）

The aim of the present study was to accurately evaluate the association of Sox2 expression with the survival of patients with digestive tract cancers. Relevant literatures were identified by comprehensively searching databases including the Pubmed, Embase, CBMdisc, and Wanfang (up to October 2014). A meta-analysis was performed to clarify the association between Sox2 expression and overall survival or clinicopathological parameters of patients with digestive tract cancers (esophageal, gastric, and colorectal cancers). The results showed a significant association between high Sox2 expression and poor overall survival in patients with digestive tract carcinomas (HR=1.55, 95% CI=1.04-2.31), especially for patients with esophageal cancer (HR=2.04, 95%CI=1.30-3.22), colorectal cancer (HR=1.40, 95% CI=1.04-1.89), and digestive tract adenocarcinoma (HR=1.80, 95% CI=1.12-2.89), for Europeans (HR=1.98, 95% CI=1.44-2.71) or patients who did not receive neoadjuvant treatment (HR=1.73, 95% CI=1.10-2.72). Furthermore, Sox2 over-expression was highly correlated with vascular invasion (OR=1.86, 95% CI=1.25-2.77) and poor differentiation (OR=1.88, 95% CI=1.14-3.08), especially in esophageal and colorectal cancers. In conclusion, Sox2 expression may serve as a novel prognostic factor for patients with digestive tract cancers. Over-expression of Sox2 that is correlated with vascular invasion and poor differentiation suggests poor outcomes of patients with digestive tract cancers.

Expressions of SOX2, TWIST, and SNAIL in breast cancer and their clinical implications / 医学研究生学报

Objective As important transcription factors, SOX2, TWIST and SNAIL are closely related to breast cancer me?tastasis. The aim of this study was to explore the expressions of SOX2, TWIST and SNAIL in breast cancer and the relationship between the three factors. Methods We collected 74 specimens of breast cancer and another 74 from paired normal tissue from January 2012 to January 2013. Using immunohistochemistry, we determined and compared the expression of SOX2 in the breast cancer and normal tissues. We also detected the expressions of TWIST and SNAIL proteins and analyzed the relationship of SOX2, TWIST and SNAIL ex?pressions with the clinicopathological characteristics of breast cancer as well as the correlation between the three proteins. Results The expression of SOX2 was significantly higher in the breast cancer than in the normal tissues (25.7% vs 8.1%, P=0.004) and corre?lated with the grade, lymph node metastasis, and TNM stage of breast cancer ( P<0.05) , while the expressions of TWIST and SNAIL were significantly correlated with lymph node metastasis and clinical TNM stages of the malignancy ( P<0.05) . The protein expression of TWIST was correlated positively with those of SOX2 ( Cc=0. 325, P<0.005) and SNAIL (Cc=0.308, P<0.008), and so was that of SNAIL with that of SOX2 (Cc=0.275, P<0.018). Conclusion The SOX2 protein is highly expressed in breast cancer. The expres?sions of SOX2, TWIST and SNAIL are closely related to lymph node metastasis of the malignancy and the three factors are interacted coor?dinatively in the metastasis of breast cancer.