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Objective:To investigate the expression of stanniocalcin-2 (STC-2) and cellular-mesenchymal epithelial transition factor (C-met) in tumor tissues of cervical cancer patients and their clinical significance.Methods:A total of 110 cervical cancer patients were selected in Foshan First People′s Hospital from January 2014 to December 2018. Patients′ cancer tissue samples and normal tissue samples were collected during modified radical resection to determine and compare the expression levels of STC-2 mRNA and C-met mRNA in the two tissues, and to analyze the correlation between the expression levels of STC-2, C-met and the clinicopathological characteristics of the patients as well as the multivariate analysis of tumor metastasis and recurrence in the patients. The correlation between the expression of STC-2 and C-met and the time of postoperative tumor metastasis and recurrence in cervical cancer patients were analyzed after 24 months of follow-up.Results:The expression levels of C-met mRNA and STC-2 mRNA in cancer tissues were higher than those in adjacent normal tissues: 4.51 ± 1.21 vs. 3.97 ± 1.14, 2.57 ± 0.21 vs. 2.12 ± 0.24, there were statistical differences ( t = 3.41, 14.80, P<0.05). The expression of STC-2 and C-met in cancer tissues had no significant difference with age, pathological type, federation international of gynecology and obstetrics (FIGO) stage and tumor size ( P>0.05), but had significant difference with tumor recurrence or metastasis ( P<0.05). The results of Logistic multivariate analysis showed that vascular emboli, lymph node metastasis, TNM stage, depth of tumor invasion, C-met expression and STC-2 expression were independent risk factors affecting the prognosis of cervical cancer patients ( P<0.05). The expression of STC-2 and C-met were negatively correlated with the time of tumor metastasis in patients with cervical cancer ( r = - 0.663, P<0.001; r = - 0.747, P<0.001). Conclusions:The expression levels of STC-2 and C-met in cancer tissues of cervical cancer patients are higher than those in adjacent normal tissues, and the expression levels of STC-2 and C-met are negatively correlated with the time of metastasis. The expression of C-met, the expression of STC-2, vascular emboli, lymph node metastasis, TNM stage, and the depth of tumor invasion are all independent risk factors affecting the prognosis of cervical cancer patients.
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Objective To explore the expression of miR-101-3p in gastric cancer and its mechanism on the invasion, metastasis, and angiogenesis of gastric cancer cells by targeting the STC-1 gene to regulate the PI3K/AKT signaling pathway. Methods qRT-PCR was used to detect the expression of miR-101-3p and STC-1 mRNA in gastric cancer tissues and BGC-823 cell and analyze the relationship between miR-101-3p expression and patients' clinical pathological factors. The cells were transfected with miRNA mimics and plasmids separately or in combination with LipofectamineTM 2000. TargetScanHuman prediction and dual-luciferase assay were used to verify the targeted regulation of miR-101-3p on STC-1. The effect and possible mechanism of miR-101-3p targeting the STC-1 gene on the invasion, metastasis, and angiogenesis of cancer cells were verified by scratch test, Transwell chamber test, Matrigel in vitro tube forming test, and Western blot assay. The development of the transplanted tumor was detected by nude mouse tumorigenicity test. Results The expression of STC-1 in gastric cancer tissues was higher than that in normal tissues. Compared with normal gastric tissues and GES-1 cells, miR-101-3p was down-regulated, and STC-1 mRNA was up-regulated in gastric cancer tissues and BGC-823 cell. The level of miR-101-3p was negatively correlated with the level of STC-1, and significantly correlated with the degree of tumor differentiation, TNM stage, and lymph node metastasis (P < 0.05). miR-101-3p directly targeted STC-1. The overexpression of miR-101-3p inhibited STC-1 expression and downregulated the expression of p-PI3K/PI3K, p-AKT/AKT, MMP-2, MMP-9, VEGF, and Ang2, consequently, inhibited tumor cell invasion, metastasis, and angiogenesis and reduced the size and weight of the transplanted tumors (P < 0.05). Conclusion miR-101-3p is down-regulated in gastric cancer and can target the STC-1 gene to regulate the PI3K/AKT signaling pathway and inhibit the invasion, metastasis, and angiogenesis of BGC-823 gastric cancer cells and the development of transplanted tumors in vivo.
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Stanniocalcin 2,a secreted glycoprotein hormone,has been found to be highly expressed in a variety of human malignancies.Through several signal transdution pathways,stanniocalcin 2 plays important roles in the regulation of many biological events of tumor such as proliferation,apoptosis,invasion and metastasis,hypoxia tolerating and drug resistance,indicating stanniocalcin 2 may be a pivotal node in the molecular regulation network of tumor.Stanniocalcin 2 is expected to become a novel biomarker and therapeutic target for diagnosis and treatment of tumor if the funtional mechanisms of stanniocalcin 2 could be further elaborated.
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AIM:To explore the effects of stanniocalcin 2 (STC2) on the proliferation, migration and the process of epithelial-mesenchymal transition (EMT) in human hepatocellular carcinoma HepG2 cells.METHODS:The expression levels of STC2 in the hepatocellular carcinoma cell lines and normal liver cells were assessed by Western blot.Colony formation assay was used to test the effect of STC2 on the proliferation of HepG2 cells.The effects of STC2 on the expression of proliferation-related molecules at mRNA and protein levels were determined by RT-qPCR and Western blot.The effect of STC2 on the migration ability was measured by Transwell assay.The mRNA and protein levels of vimentin and E-cadherin in STC2-overexpressing and-silencing cell lines were detected by RT-qPCR and Western blot.RESULTS:Compared with the normal liver cell line, the protein expression of STC2 was up-regulated in the hepatocellular carcinoma cell lines.The results of colony formation assay indicated that STC2 promoted the proliferation of HepG2 cells.STC2 significantly regulated the proliferation-related gene expression, such as cyclin D1.The results of Transwell assay showed that STC2 enhanced the migration ability of the HepG2 cells and influenced the EMT process.CONCLUSION:STC2 promotes the proliferation of HepG2 cells and affects the expression of proliferation-related genes.STC2 influences the process of EMT and promotes the migration of HepG2 cells.
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Objective To study the effect of STC2 on invasion and metastasis of breast cancer cells and its mechanism.Methods By 231 HM shRNA interference cell STC2,we observed fiber cells expressing form,number plate cloning experiment statistical analysis.Immune co-precipitation (CO-IP) for testing related protein expression.Results By 231 HM STC2 cells expressing shRNA interference,231 HM presents high transfer characteristics of fiber cell morphology,cell invasion and metastasis ability of increase at the same time;On the contrary,after 231 cells expressing STC2,cell invasion and metastasis ability induced.In addition,after reducing STC2 expression of 231 HM cells,its resistance to radiation-inducled apoptosis and expression of STC2 after 231 reduced,ability to resist radiation induced apoptosis of cells induled too.Conclusion Collectively,these results indicate that STC2 may inhibit EMT at least partially through the PKC/Claudin-1-mediated signaling in human breast cancer cells.
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Objective To investigate the protein expression of stanniocalcin 1 (STC1) in papillary thyroid carcinoma (PTC) in gerontal patients versus non-gerontal subjects,and its relationship with clinicopathological features.Methods The protein expression levels of STC1 in PTC,nodular goiter and normal thyroid tissues in the gerontal patients versus non-gerontal subjects were detected by immunohistochemistry.The protein expressions of STC1 were detected by Western blotting.Results The protein expression of STC1 in gerontal patients was higher in PTC than in nodular goiter and normal thyroid tissues (60.9％ vs.30.0％,15.0％,P＜0.05 or 0.01).The relative expression of STC1 protein in gerontal patients was higher in PTC than in nodular goiter and normal thyroid tissues [(0.647 ± 0.076) vs.(0.280 ± 0.039),(0.248 ± 0.065),F =9.965 and 1.143,both P＜0.01].STC1 protein expression had no correlations with age,gender,tumor diameter and tumor position in patients (P＜0.05),while it was associated with tumor lymph node metastasis and clinical stage (P＜0.05).There was no significant difference in above indexes between the elderly and non-elderly patients with papillary thyroid carcinoma (F=0.007,P=0.934).Conclusions STC1 protein may be associated with the development of papillary thyroid carcinoma,and it may has a some reference value in differentiating benign from malignant thyroid neoplasms and in predicting the prognosis of thyroid carcinomas.
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Stanniocalcin (STC) was ifrst found as a calcium- and phosphate-regulating hormone produced in bony ifsh by the corpuscles of Stannius. In mammals, the homolog STC-1 displays a relative high amino acid sequence identity (nearly 50%) with ifsh STC, and STC-2 has a lower identity (nearly 35%) with STC-1 and ifsh STC. Both STC-1 and STC-2 are expressed in a variety of tissues. The functions of STC have not been understood. But some ifndings have been reported on their cellular localization, gene structure, and expression in different physiological and pathological conditions, which will be clues in elucidating the functions of STC in mammals. Moreover, STC-1 and STC-2 are expressed in many tumor cell lines, suggesting other biological functions of STC in mammals other than mineral metabolism.
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Background and purpose:Stanniocalcin 1 (STC1) has been reported to be up-regulated in various cancer tissues, and related to malignancy degree of cancer. However, the molecular mechanism of STC1 in lung cancer cells is still not clear. This experiment aimed to investigate the effects of STC1 on cell cycle and apoptosis of lung cancer A549 cells.Methods:A549 cells were transfected with validated siRNA for STC1 A549-STC1-siRNA and a negative control vector RNA A549-Vector. The gene and protein expression of cell cycle-related genes, including CyclinA, CyclinB1, CyclinD1, CyclinE, CDK2 and CDK4, as well as apoptosis-inhibiting genes Bcl-2, Bcl-xl and apoptosis-inducing genes Caspase-3, Bax, Bak and Bid, were detected by real-time lfuorescent quantitative polymerase chain reaction (RTFQ-PCR) and Western blot. The cell cycle distribution was determined with lfow cytometry. Terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) was used to detect cell apoptosis.Results:After transfection with STC1-siRNA, the gene and protein expression of CyclinA, CyclinB1, CyclinD1, CyclinE, CDK2 and CDK4 decreased signiifcantly in A549 cells (P whereas the proportion of cells in S phase and G2/M phase decreased (P<0.05). The cell cycle was blocked at G0/G1 phase. Furthermore, compared with that in A549-Vector, the gene and protein expression of Bcl-2 and Bcl-xl in A549-STC1-siRNA was reduced signiifcantly (P<0.05), while the expression of apoptosis-inducing genes Caspase-3, Bax, Bak and Bid increased obviously (P<0.05). In addition, the percentage of apoptotic cells significantly increased in A549-STC1-siRNA compared with that in A549-Vector detected by TUNEL method.Conclusion:Down-regulation of STC1 by RNAi can block the cell cycle of A549 cells, inhibit cell proliferation, and promote cell apoptosis.
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Renal cell carcinoma (RCC) is one of the most lethal malignancies of the urinary system, however, its pathogenic mechanism is not clear.Stanniocalcin (STC) is a type of glycoprotein hormone with multiple biological functions.Recently, the role of STC in the pathogenesis of cancer is of intriguing interest, and many researches have been performed to clarify underlying mechanism. We emphasized the role of STC in the underlying mechanism of RCC progression, from the aspects of STC inducing hypoxia adaptation of tumor cells, promoting tumor angiogenesis, also promoting cell proliferation, apoptosis, invasion and metastasis, and inhibiting the immune response.Conclusively, STC could be used as both a promising biomarker for RCC diagnosis and a theraputic target of renal cell carcinoma.
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Aims: The acquired cholesteatoma, even with all the knowledge accumulated since its first description, still remains a public health problem, far from being solved. A deeper understanding of its pathogenesis is extremely important since it is a destructive lesion that might cause potentially serious complications. We had the objective, in this study, to identify acquired cholesteatoma biomarkers using proteomics platform. Study Design: descriptive cross-sectional study. Methodology: Samples were collected from cholesteatoma and also from the retroauricular skin of twelve patients undergoing surgery for cholesteatoma removal. The samples were studied by proteomic analysis, using the Mascot algorithm and the NCBI and Swiss Prot proteins database. Results: Of the 393 spots identified in the analysis of protein extracts of acquired cholesteatoma, only 10 were within acceptable statistical parameters by Mascot algorithm. The proteins detected in acquired cholesteatoma were fibrinogen beta chain, extracellular matrix protein 2, actin cytoplasmic 1, heparan sulfate glucosamine 3-O-sulfotransferase 3A1, tumor necrosis factor alpha 8 induced protein-like 1, stanniocalcin-2, eosinophil lysophospholipase and OFUT1. Conclusion: Proteins involved in cell migration, regulation of apoptosis, signaling pathways, cellular proliferation, wound healing and inflammatory processes were identified. We were able to draw a proteomic profile of acquired cholesteatoma.
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Chronic enteritis can produce an excess of reactive oxygen species resulting in cellular damage. Stanniocalcin-1(STC-1) reportedly possesses anti-oxidative activity, the aim of this study was to define more clearly the direct contribution of STC-1 to anti-oxidative stress in cattle. In this study, primary intestinal epithelial cells (IECs) were exposed to hydrogen peroxide (H2O2) for different time intervals to mimic chronic enteritis-induced cellular damage. Prior to treatment with 200 microM H2O2, the cells were transfected with a recombinant plasmid for 48 h to over-express STC-1. Acridine orange/ethidium bromide (AO/EB) double staining and trypan blue exclusion assays were then performed to measure cell viability and apoptosis of the cells, respectively. The expression of STC-1 and apoptosis-related proteins in the cells was monitored by real-time PCR and Western blotting. The results indicated that both STC-1 mRNA and protein expression levels positively correlated with the duration of H2O2 treatment. H2O2 damaged the bovine IECs in a time-dependent manner, and this effect was attenuated by STC-1 over-expression. Furthermore, over-expression of STC-1 up-regulated Bcl-2 protein expression and slightly down-regulated caspase-3 production in the damaged cells. Findings from this study suggested that STC-1 plays a protective role in intestinal cells through an antioxidant mechanism.
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Animals , Cattle , Male , Animals, Newborn , Blotting, Western/veterinary , Caspase 3/genetics , Cattle Diseases/etiology , Duodenum/metabolism , Enteritis/etiology , Epithelial Cells/metabolism , Gene Expression Regulation , Glycoproteins/genetics , Hydrogen Peroxide/pharmacology , Proto-Oncogene Proteins c-bcl-2/genetics , RNA, Messenger/genetics , Real-Time Polymerase Chain Reaction/veterinaryABSTRACT
Objective To obtain recombinant human stanniocalcin 1 ( STC1 ) with biological activity in Escheri.coli cells expression.Methods The gene was cloned into pET32b( +) vector by fused with thioredoxin and His tag .E.coli BL21(DE3) competent cells were transfomed by the recombinant vector .After renaturation, the fusion protein was digested with thrombin and intact STC1 protein was purified from the digested protein using Ni ion affinity chromatography .Recombi-nant humanSTC1 protein was confirmed by Western blot analysis using goat anti-STC1 antibody.The biological activity of STC1 in rat was assayed using standard method for assessment of renal function .Results The recombinant human STC 1 fu-sion protein is successfully expressed in Escherichia coli, the fusion protein was purified by affinity chromatography from the inclusion body and renaturated .Intact hSTC1 protein was released by thrombin digestion and purified by Ni ion affinity col-umn.The intact STC1 proteins was confirmed by Western blot analysis .Rat bioassay revealed that STC1 boosted phosphate reabsorption.Conclusion Recombinant STC1 protein was successfully expressed and has native biological activities .This protein could be used as an antigen for the preparation of monoclonal antibody against humanSTC 1.
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Objective To observe the change of stanniocalcin 1 (STC1) and calcium content in brain of coal-burning-borne fluorosis rats,and to explore the role of STC1 in brain injury of coal-burning-borne fluorosis.Methods Twenty four male SD rats were randomly divided into control,low,medium,and high fluoride groups according to body mass.Control group was fed conventional rat chow(fluorinated 1.3 mg/kg),and low,medium and high fluoride groups fed with fluorinated feed(20.0,40.0,60.0 mg/kg).All rats were given distilled water and feed ad libitum.One hundred and eighty days after modeling,STC1 protein and gene expression in the brain tissue of rats were detected using immunohistochemistry and RT-PCR and calcium content of brain tissue was detected.Results The cell positive rates of STC1 in low,medium,high fluoride groups [(48.10 + 2.11)％,(54.90 ± 1.73)％,(79.30 ± 3.71)％] were significantly higher than that of the control group[(24.70 + 3.53)％,all P ＜ 0.05],the cell positive rate of high fluoride group was significantly higher than that of the low and medium fluoride groups (all P ＜ 0.05).The STC1 mRNA expression of low,medium and high fluoride groups (0.58 ± 0.09,0.85 ± 0.17,1.75 ± 0.04) were significantly higher than that in the control group(0.37 ± 0.12,all P＜ 0.05),the STC1 mRNA expressions of high fluoride group was significantly higher than that of the low and medium fluoride groups (all P ＜ 0.05).The brain cortex calcium ion concentrations of low,medium and high fluoride groups[(138.62 + 4.19),(167.43 + 6.57),(189.45 + 3.72)nmol/L] were significantly higher than that in the control group [(101.47 + 9.46)nmol/L,all P ＜ 0.05],the brain cortex calcium ion concentrations of high fluoride group was significantly higher than that of the low and medium fluoride groups(all P ＜ 0.05),and the medium fluoride groups was higher than the low groups (P ＜ 0.05).Conclusion STC 1 may be involved in brain damage of coal-burning-borne fluorosis rats through regulating calcium balance.
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OBJECTIVE: Stanniocalcin 2 (STC2) is a glycoprotein hormone that is widely expressed in mammalian kidney, heart, and thymus. However, the potential function of STC2 in the brain is less understood. In this study, we investigated whether treatment with STC2 influenced cell proliferation and neurogenesis in imprinting control region (ICR) mice. METHODS: 100 nM STC2 and 5'-bromo-2'-deoxyuridine (BrdU) (50 mg/kg) were administered intracerebroventricularly and intraperitoneally, respectively. On days 1 and 21 after the BrdU injection, sections of STC2-treated group and controls were carried out immunohistochemistry using anti-BrdU and anti-phosphor-cAMP-response element-binding protein (CREB) antibody. RESULTS: We found that the number of BrdU-positive cells was significantly increased in the hippocampal dentate gyrus (DG), compared with controls. Next, we observed that CREB phosphorylation was decreased in the hippocampal DG of STC2-treated group versus the controls. CONCLUSION: These results suggest that STC2 treatment may increase cell proliferation by increasing CREB phosphorylation in the subgranular zone of the DG.
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Animals , Mice , Brain , Bromodeoxyuridine , Cell Proliferation , Dentate Gyrus , Depression , Glycoproteins , Heart , Hippocampus , Immunohistochemistry , Kidney , Mice, Inbred ICR , Neurogenesis , Phosphorylation , Thymus GlandABSTRACT
Objective: To detect the expression of human stanniocalcin-1 (hSTC-1) mRNA in peripheral blood and tumor tissues of breast cancer patients, determine micrometastases in peripheral blood, and study the relationship between the micrometastases and malignant degree of breast cancer. Methods: The expression of hSTC-1 mRNA in peripheral blood and breast cancer tissues was detected by RT-PCR. The expression of estrogen receptor (ER), progesterone receptor (PR), and vascular endothelial growth factor (VEGF) in breast cancer tissues were detected by immunohistochemical method. Results: Expression of hSTC-1 mRNA was identified in breast cancer tissues from 28 of 30 patients (93.3%) and in peripheral blood from 19 of 51 patients (37.3%). Expression of hSTC-1 mRNA was not detected in the peripheral blood from 17 women without breast cancer. Expression of hSTC-1 mRNA in the peripheral blood significantly correlated with multiple clinicopathological factors (P < 0.05), including tumor size, metastasis of lymph nodes, TNM stage, and the expression of ER and VEGF. Conclusion: The expression of hSTC-1 mRNA in the peripheral blood of breast cancer patients suggests the occurrence of micrometastasis. It significantly correlates with multiple clinicopathological factors which determined the prognosis of breast cancer. So hSTC-1 is proposed as a new marker for detecting micrometastasis of breast cancer in the peripheral blood.
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Objective To study the relationship between the expression of human Stanniocalcin-1(hSTC-1) mRNA in the peripheral blood from patients with colorectal cancer and its malignant behavior. Methods RT-PCR was used to detect hSTC-1 mRNA in the peripheral blood from 57 patients with colorectal cancer. The peripheral blood from 14 patients with gastrointestinal inflammatory diseases, 15 healthy volunteers and 5 pregnant women were served as controls. Results The positive rate of hSTC-1 mRNA in 57 patients with colorectal cancer was 49.12% (28/57), and the mRNA expression of hSTC-1 was significantly related with the clinical stage of colon cancer (P
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Stanniocalcin(STC) is a glycoprotein hormone that was firstly found in bony fish.The related human proteins,STC1and STC2,are expressed in a wide variety of tissues.STC1 is involved in calcium and phosphate homeostasis,and plays important roles in carcinogenesis.This article reviews the data currently available regarding the human STC1,and discusses the roles they may play in normal physiology and in cancers.