Shu-Tao Zheng

Xinjiang Medical University, Ouroumtchi, Xinjiang Uygur Zizhiqu, China

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Publications (11)19.05 Total impact

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    ABSTRACT: To investigate the role of p38αmitogen-activated potein kinases (MAPK) in human esophageal squamous cell carcinoma cell line Eca109. Specific short hairpin (shRNA) vector as well as eukaryotic expression vector harbouring full length cDNA of human p38α MAPK were transfected into Eca109 cells. Cell proliferation after transfection was detected by MTT, cell cycle and apoptosis were assayed by flow cytometry. The variation of migration and invasion after tranfection was determined using wound healing assay and Transwell assay, respectively. The proliferation of Eca109 cells after knock-down for 48 h (0.951 ± 0.086) was significantly increased (t = 3.20, P < 0.05) compared with control (0.811 ± 0.012), Sphase was increased but not significantly. Cell apoptosis rate after knock down for 48 h (17.400 ± 5.495) was significantly increased (t = 40.06, P < 0.01) compared with control(1.000 ± 0.721) . Migration after knock down for 72 h (0.034 ± 0.031) were enhanced pronouncedly (t = -5.79, P < 0.01) compared with control (0.278 ± 0.021) and invasive ability also increased; whereas the proliferation of Eca109 cells after over-expression for 48 h (0.472 ± 0.089) was inhibited significantly (t = -7.50, P < 0.01) compared with control(0.811 ± 0.012), cells arrested at G1 phase (t = 4.80, P < 0.01). Cell apoptosis rate (32.233 ± 1.457) were decreased significantly (t = 17.20, P < 0.01) compared with control (1.000 ± 0.721) mm, migration after overexpression for 72 h ((0.770 ± 0.054) mm) was suppressed pronouncedly compared with control groups of (0.278 ± 0.021) mm(t = 11.00, P < 0.01).Invasion after overexpression was inhibited. p38α MAPK plays an anti-oncogenic role in the pathogenesis of esophageal squamous cell carcinoma cell line Eca109.
    Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine] 08/2013; 47(8):757-761.
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    ABSTRACT: The p38 mitogen-activated protein kinase (MAPK) is a member of the MAPK family, which is initially found to be activated by stress stimuli, proinflammatory cytokines, and growth factors. However, its role in the pathogenesis of esophageal squamous cell carcinoma (ESCC) is largely unkown, so we investigate the role of phosphorylated p38 (p-p38) MAPK in ESCC. First of all, in vitro cell line ECa109, SB203580 as selective inhibitor of p38, can suppress the growth of esophageal cancer cell in a dose- and time-dependent way, suggesting that ECa109 cell growth and proliferation was closely associated with p-p38. Using western-blot analysis of fresh 16 paired surgically resected ESCC and matched non-tumor adjacent tissues (NAT), we showed that p-p38 was significantly expressed higher in NAT compared to ESCC. Moreover, expressions of p-p38 were further confirmed by 162 paired of formalin-fixed paraffin-embedded (FFPE) ESCC and NAT by immunohistochemistry, the same trend result was obtained through statistical analysis that there was increased expression of p-p38 in NAT as compared with ESCC (P < 0.01), and expression of p-p38 was not significantly associated with lymph nodes metastasis (P > 0.05) and ESCC differentiation degree (P > 0.05). Taken together, all the results we obtained demonstrated that p-p38 plays a key role in the malignant transformation of ESCC.
    Molecular Biology Reports 12/2011; 39(5):5315-21. DOI:10.1007/s11033-011-1330-0 · 2.02 Impact Factor
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    ABSTRACT: To investigate the expression variation and significance of ERK1/2 MAPK signaling transduction pathway in the pathogenesis of esophageal squamous cell carcinoma (ESCC) in Kazakh patients. The expression level of p-ERK1/2 after serum starvation and treatment with U0126 inhibitor was detected in esophageal cancer cell line EC9706 by Western blot assay. The mRNA level of total ERK1/2 (t-ERK1/2) and expression level of t-ERK1/2 and p-ERK1/2 proteins of 25 pairs of ESCC and adjacent normal esophageal mucosal tissues of Kazakh patients were examined and identified by real-time quantitative PCR (qRT-PCR) and Western blotting, respectively. The expression of p-ERK1/2 protein was verified by immunohistochemistry in 126 paraffin-embeded specimens, including 19 normal esophageal mucosa, 55 esophageal carcinomas in situ and 52 invasive carcinomas. ERK1/2 MAPK signaling transduction pathway was in an active status in the EC9706 cells. The expression level of p-ERK1/2 in Ec9706 cells reached a peak at 10 min after transient serum stimulation, and p-ERK1/2 expression was totally restrained after the treatment with 50 µmol/L U0126. In the 25 pairs of ESCC and adjacent normal mucosa, the t-ERK1 mRNA level was 1.92 ± 3.49 in the ESCC tissues and 3.67 ± 7.47 in the adjacent normal mucosa. The t-ERK1 mRNA level in ESCC tissues was significantly lower than that in adjacent normal mucosa (P < 0.05), whereas there was no significant difference of t-ERK2 mRNA level between them(P > 0.05). The expression levels of p-ERK1 and p-ERK2 proteins were 0.87 ± 0.14 and 0.79 ± 0.10 in the ESCC tissues, and 1.10 ± 0.13 and 1.32 ± 0.12 in the adjacent normal mucosae. p-ERK1/2 protein in the ESCC tissues was significantly lower than that in the adjacent normal tissue (P < 0.01). However, there was no significant difference between their t-ERK1/2 protein levels (P > 0.05). In the 126 cases of paraffin-embeded specimens, positive expressions of both p-ERK1 and p-ERK2 in esophageal cancer tissues were 7.7% (4/52), significantly lower than those in adjacent normal mucosa (31.6%, 6/19) and carcinoma in situ (85.5%, 47/55, P < 0.05). ERK1/2 MAPK signaling pathway is in an active status in esophageal cancer and adjacent normal mucosa. Our results imply that the activation of p-ERK1/2 MAPK signaling transduction pathway plays a role in the early pathogenesis of ESCC in Kazakh patients.
    Zhonghua zhong liu za zhi [Chinese journal of oncology] 06/2011; 33(6):421-5. DOI:10.3760/cma.j.issn.0253-3766.2011.06.005
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    ABSTRACT: Annexin A2 and Cdc42 were identified by 2-dimensional electrophoresis (2-DE) and MALDI-TOF-MS between esophageal squamous cell carcinomas (ESCC) and corresponding normal esophagus mucosa in our previous study. To assess clinico-pathological pattern and Annexin A2 and Cdc42 status with respect to cell differentiation and lymphnode metastasis in patients with ESCC. The expression of Annexin A2 and Cdc42 in 22 pairs of fresh ESCC and matched tissues were detected by qRT-PCR and western blot, respectively. And it was further confirmed by immunohistochemistry with 175 pairs of formalin-fixed, paraffin-embedded ESCC. Results showed that Annexin A2 expression was significantly down-regulated, and Cdc42 was up-regulated in ESCC compared to matched control on both mRNA and protein level (P < 0.05), which was in accordance with our previous results on proteomics data. Additionally, Annexin A2 and Cdc42 expression was significantly correlated with lymphoid node metastasis (P < 0.05) and pathological differentiation (P < 0.05). Taken together, we proposed that the aberrant expression of Annexin A2 and Cdc42 played a role in carcinogenesis, differentiation and metastasis of ESCC, which implied its potential target for clinical biomarkers in differentiation and lymph node metastasis.
    Molecular Biology Reports 05/2011; 39(2):1267-74. DOI:10.1007/s11033-011-0859-2 · 2.02 Impact Factor
  • Qing Liu · Guo-Dong Lv · Xu Qin · Yue-Hua Gen · Shu-Tao Zheng · Tao Liu · Xiao-Mei Lu ·
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    ABSTRACT: To investigated the role of microRNA (miRNA) let-7 and its regulation on high mobility group A2 (HMGA2) protein expression in esophageal squamous cell carcinoma (ESCC). Let-7 expressions were detected in esophageal cancer cell line Eca109, and 45 paired of fresh ESCC and normal adjacent tissues (NAT) by real-time quantitative PCR (qRT-PCR). To evaluate the role of let-7 and HMGA2, cell proliferations were analyzed with synthetic let-7 mimics- or its inhibitor-transfected cells. Moreover, expressions of HMGA2 were performed by western blotting and further confirmed by 150 paired of formalin-fixed, paraffin-embeded (FFPE) ESCC and NAT by immunohistochemistry (IHC). In Eca109, when transfected with let-7 mimics, accumulation of let-7 was obviously suppressed cell proliferation with approximately 14%. Conversely, when Eca109 transfected with let-7 inhibitor, expression of let-7 was declined, which promoted cell proliferation with approximately 16%. Both of them had no effect on the level of HMGA2 mRNA. The transcription of let-7 inversely correlated with HMGA2 protein. Compared with the NAT, expression of let-7 was significantly lower in ESCC tissues (P < 0.05), and there was a significant correlation between low expression of let-7 and lymph node metastasis in ESCC (P < 0.05). Moreover, the protein expression of HMGA2 was significantly higher in ESCC compared with NAT (P < 0.05). However, mRNA expression of HMGA2 had no obvious significance between them. The present results demonstrated that let-7 and HMGA2 involved in ESCC carcinogenesis. Let-7 could inhibit cell proliferation and lower expressed in ESCC, and there was a correlation between let-7 lower expression and lymph node metastasis in ESCC patients. As well as, HMGA2 protein expression was significantly higher in ESCC than that in NAT, and HMGA2 may negatively regulated by let-7 at the post- transcriptional level in ESCC.
    Molecular Biology Reports 05/2011; 39(2):1239-46. DOI:10.1007/s11033-011-0854-7 · 2.02 Impact Factor
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    ABSTRACT: The Objective is to identify candidate biomarkers for Squamous cell carcinoma (ESCC) in three ethnics in Xinjiang as well as reveal molecular mechanism. Proteins from 15 pairs of ESCC and matching adjacent normal esophageal tissues (five pairs in each ethnic of Kazakh, Uygur and Han) were separated by 2-DE and differentially proteins were identified by matrix-assisted laser desorption/ionization time-of-flight MS. After identified by Mascot database, some of interesting proteins were confirmed in the other 175 pairs of ESCC by immuno histochemistry. Comparison of patterns revealed 20 proteins significantly changed, of which 12 protein with concordantly increased, such as ACTB protein, COMT protein, Syntaxin binding protein Pyruvate Kinase (PKM2), Cathepsin D, Chromosome 1 open reading frame 8, Heat shock protein 27, Cdc42, Proteosome, LLDBP, Immunoglobulin, TNF receptor associated factor 7; and eight protein spots with concordantly decreased intensity in ESCC, such as Adenylate kinase 1, General transcription factor II H, Smooth muscle protein, Trangelin, Early endosome antigen 1, Annexin A2, Fibrin beta, Tropomyosin. There were a significant difference in protein overexpression of PKM2 (74.9%) and Cathepsin D (85.1%) in ESCC compared to adjacent tissues (P < 0.05) by immunohistochemistry. Further, overexpression of Cathepsin D was obvious difference in Hazakh ESCC (94.7%) than that in Uygur (78.6%) (P < 0.05). Interestingly, the overexpression of Cathepsin D was reversely associated with ESCC differentiation (P < 0.05). Twenty proteins differentially-expressed between ESCC and normal tissues were identified. Cathepsin D and PKM2 were for the first time observed to be dysregulated in Kazakh's ESCC. Moreover, Cathepsin D may play a complicated role both in carcinogenesis and cell-differentiation of ESCC.
    Molecular Biology Reports 12/2010; 38(5):3261-9. DOI:10.1007/s11033-010-0586-0 · 2.02 Impact Factor
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    ABSTRACT: The aim of this study was investigate the role of microRNA-21 (miR-21) and its regulation on phosphatase and tensin homolog deleted from chromosome-10 (PTEN) in Kazakh's esophageal squamous cell carcinoma (ESCC). MiR-21 expressions were investigated in esophageal cancer cell line Eca109, and 18 pairs of Kazakh's ESCC and adjacent normal tissues by real-time quantitative PCR (qRT-PCR). To evaluate the role of miR-21 and PTEN, cell proliferations were analyzed with miR-21 mimics or their inhibitor-transfected cells. Moreover, the expressions of PTEN were performed by Western blotting. In Eca109, when transfected with miR-21 mimics, accumulation of miR-21 was obviously increased and expression of PTEN protein was decreased to be approximately 40%, which resulted in the promotion of cell proliferation. However, when transfected with miR-21 inhibitor, expression of miR-21 was declined and PTEN protein was overexpressed to be approximately 79%, which resulted in the suppression of cell proliferation. Both of them had no effect on the level of PTEN mRNA. Compared with adjacent normal tissues, miR-21 expression was significantly higher in tumor (P < 0.05). Specifically, patients with cancer cell invasion deep into esophageal serosa showed significantly higher expression of miR-21. Protein expression of PTEN was significantly lower in tumor compared with normal tissues (P < 0.05); however, mRNA expression of PTEN had no obvious significance between them. Furthermore, there was a significantly inverse correlation between miR-21 expression and PTEN protein levels (p < 0.05). The author concluded that MiR-21 was overexpressed in vitro and ESCC, and promoted the cell proliferation, might target PTEN at post-transcriptional level, and regulated the cancer invasion in Kazakh's ESCC.
    Molecular Biology Reports 11/2010; 38(5):3253-60. DOI:10.1007/s11033-010-0480-9 · 2.02 Impact Factor
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    ABSTRACT: Esophageal squamous cell carcinoma is one of the most common digestive tract cancers with 5-year survival rate less than 10% owing to its poor prognosis. Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signaling pathway has been mainly involved in the pathogenesis of various cancers. In present study, we investigated the role of ERK2 in human esophageal cancer cell line Eca109. Short-hairpin RNA (shRNA) interference vector targeted ERK2 was constructed using pGeneclip U1 hairpin cloning systems, then transfected into Eca109 cell line. The transfection efficiency was observed by fluorescence microscope and cell growth after transfection with shRNA-ERK2 vector was determined by methylthiazolyl blue tetrazolium (MTT) assay. The ERK2 expression after transfection was detected by western-blotting. The cell apoptosis and cell-cycle was analyzed by flow cytometry. The role of p-ERK2 was confirmed by immunohistochemistry and soft agar colony formation assay. The growth of Eca109 transfected with shRNA-ERK2 vector was obviously inhibited compared to control group via MTT analysis. The inhibition rate after transfection with shRNA-ERK2 for 96 h was 10.45%, the expression of ERK2 was obviously reduced compared to the control analyzed by western-blot, cell apoptosis was 9.7% (compared to control, P < 0.05), and cell-cycle was arrested at G1 phase. In present study we demonstrated for the first time that transfection with shRNA-ERK2 targeted ERK2 into Eca109 cells can inhibit growth of Eca109, inducing cell apoptosis and influencing cell-cycle. Together, these results we obtained suggested that ERK2 plays an important role in cell growth of Eca109.
    Journal of Receptor and Signal Transduction Research 06/2010; 30(3):170-7. DOI:10.3109/10799891003786200 · 2.28 Impact Factor
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    ABSTRACT: While there have been more and more studies concerning mitogen-activated protein kinases (MAPKs) signaling pathways, which control many cellular complex programmes, such as cell proliferation, differentiation, cell death and embryogenesis. However, few studies are carried out about expression and activation of classical MAPKs, extracellular signal-regulated kinase1/2 (ERK1/2) in human esophageal cancer cell line. Therefore, in the present study, we investigated the expression and activation of ERK1/2 in human esophageal cancer cell line EC9706 and human normal esophageal epithelial cell line Heepic, which is as control. This study showed that ERK1/2 was transiently phosphorylated both in EC9706 and Heepic, the kinetics of which were slightly different. To further study the ERK/MAPK signaling pathway in EC9706 and Heepic cell line, U0126 a kind of specific inhibitor of MEK was used. This study showed that U0126 can block the phosphorylation of ERK1/2 in a short time, the complete inhibition concentration for EC9706 and Heepic cell line is 50 and 20 μM, respectively. Incidentally, to further investigate the different roles of ERK1 and ERK2, vector-based short hairpin interference vectors targeted on ERK1/2 was constructed. Moreover, the effective interference target sequence was screened out in a transient transfection manner. MTT experiment showed that ERK2 is more important than ERK1 in the proliferation of EC9706 cells.
    Molecular Biology Reports 05/2010; 38(2):865-72. DOI:10.1007/s11033-010-0178-z · 2.02 Impact Factor
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    ABSTRACT: To investigate the role of metabolic enzyme and DNA repair genes in susceptibility of esophageal squamous cell carcinoma (ESCC). A case-control study was designed with 454 samples from 128 ESCC patients and 326 gender, age and ethnicity-matched control subjects. Genotypes of 69 single nucleotide polymorphisms (SNPs) of metabolic enzyme (aldehyde dehydrogenase-2, ALDH2; alcohol dehydrogenase-1 B, ADHB1; Cytochrome P450 2A6, CYP2A6) and DNA repair capacity genes (excision repair cross complementing group 1, ERCC1; O(6)-methylguanine DNA methyltransferase, MGMT; xeroderma pigmentosum group A, XPA; xeroderma pigmentosum group A, XPD) were determined by the Sequenom MassARRAY system, and results were analyzed using unconditional logistic regression adjusted for age, gender. There was no association between the variation in the ERCC1, XPA, ADHB1 genes and ESCC risk. Increased risk of ESCC was suggested in ALDH2 for frequency of presence C allele of SNP [Rs886205: 1.626 (1.158-2.284)], XPD for C allele [Rs50872: 1.482 (1.058-2.074)], and MGMT for A allele [Rs11016897: 1.666 (1.245-2.228)]. Five variants of MGMT were associated with a protective effect on ESCC carcinogenesis, including C allele [Rs7069143: 0.698 (0.518-0.939)], C allele [Rs3793909: 0.653 (0.429-0.995)], A allele [Rs12771882: 0.719 (0.524-0.986)], C allele [Rs551491: 0.707 (0.529-0.945)], and A allele [Rs7071825: 0.618 (0.506-0.910)]. At the genotype level, increased risk of ESCC carcinogenesis was found in homozygous carriers of the ALDH2 Rs886205 [CC vs TT, odds ratios (OR): 3.116, 95% CI: 1.179-8.234], MGMT Rs11016879 (AA vs GG, OR: 3.112, 95% CI: 1.565-6.181), Rs12771882 (AA vs GG, OR: 2.442, 95% CI: 1.204-4.595), and heterozygotes carriers of the ALDH2 Rs886205 (CT vs TT, OR: 3.930, 95% CI: 1.470-10.504), MGMT Rs11016879 (AG vs GG, OR: 3.933, 95% CI: 2.216-6.982) and Rs7075748 (CT vs CC, OR: 1.949, 95% CI: 1.134-3.350), respectively. Three variants were associated with a protective effect on ESCC carcinogenesis, carriers of the MGMT Rs11016878 (AG vs AA, OR: 0.388, 95% CI: 0.180-0.836), Rs7069143(CT vs CC, OR: 0.478, 95% CI: 0.303-0.754) and Rs7071825 (GG vs AA, OR: 0.493, 95% CI: 0.266-0.915). Increased risk of ESCC metastasis was indicated in MGMT for frequency of presence C allele [Rs7068306: 2.204 (1.244-3.906)], A allele [Rs10734088: 1.968 (1.111-3.484)] and C allele [Rs4751115: 2.178 (1.251-3.791)]. Two variants in frequency of presence C allele of CYP2A6 [Rs8192720: 0.290 (0.099-0.855)] and A allele of MGMT [Rs2053139: 0.511 (0.289-0.903)] were associated with a protective effect on ESCC progression. Increased risk of ESCC metastasis was found in heterozygote carriers of the MGMT Rs7068306 (CG vs CC, OR: 4.706, 95% CI: 1.872-11.833). Polymorphic variation in ALDH2, XPD and MGMT genes may be of importance for ESCC susceptibility. Polymorphic variation in CYP2A6 and MGMT are associated with ESCC metastasis.
    World Journal of Gastroenterology 02/2010; 16(5):641-7. DOI:10.3748/wjg.v16.i5.641 · 2.37 Impact Factor
  • Shu-Yong Xu · Zan Liu · Wen-Jing Ma · Ilyar Sheyhidin · Shu-Tao Zheng · Xiao-Mei Lu ·
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    ABSTRACT: To analyse the alterations of serum proteins in cases of esophageal squamous cell carcinoma (ESCC) in order to screen and validate serum marker patterns for the diagnosis of ESCC in the high-risk populations of Xinjiang, China. The serum proteomic patterns of 188 cases, including 139 patients with ESCC (54 Uygur, 45 Kazakh and 40 Han subjects) and 49 sex- and age-matched healthy controls, were detected using the SELDI-TOF-MS (surface-enhanced laser desorption/ionization-time of flight-mass spectrometry) technology with the CM10 ProteinChip. Differences in protein peaks between patients with ESCC and controls were analysed using the Biomarker Pattern Software, and a primary diagnosis model of ESCC was developed and validated with SVM (support vector machines). This model was further evaluated by a large-scale blind test. Two hundred and eighty-three protein peaks were detected within the molecular range of 0-20 kDa, among which, 140 peaks were significantly different between ESCC cases and controls (p < 0.05). A diagnostic pattern consisting of six protein peaks (m/z 5667, 5709, 5876, 5979, 6043 and 6102) was established with a sensitivity of 97.12% and a specificity of 83.87%. The large-scale blind test generated a sensitivity of 91.43% and a specificity of 88.89%. The differential protein peaks analysed by SELDI-TOF-MS may contain promising serum biomarkers for screening ESCC. The diagnostic model which combined only six protein peaks had a satisfactory discriminatory power. The model should be further evaluated in other populations of ESCC patients and tested against controls. The nature and function of the discriminating proteins have yet to be elucidated.
    Biomarkers 04/2009; 14(5):340-6. DOI:10.1080/13547500902903055 · 2.26 Impact Factor