Downregulation of long noncoding RNA CASC15 inhibits progression, migration and invasion of papillary thyroid cancer.

Introduction: Thyroid cancers are the most common malignancy of the endocrine system. Increasing evidence has suggested potential roles for cancer susceptibility candidate 15 (CASC15) in thyroid cancer. Papillary thyroid cancer (PTC) accounts for 80% of thyroid cancer, posing a great threat to public health. The present study aims to investigate the potential roles of CASC15 in PTC. Material and methods: PTC tissues were obtained from patients diagnosed with PTC at the Second Hospital of Hebei Medical University from October 2016 to January 2018. qRT-PCR was performed to examine the mRNA levels of CASC15, Bcl-2/BAX, E-cadherin, caspase-3, and PI3K/AKT. Western blotting was applied to determine the protein levels of PI3K/AKT, CASC15, E-cadherin, BAX, Bcl-2 and caspase-3. CCK-8 assays were used to determine the viability of BCPAP and K1 cancer cells. Wound healing and transwell assays were conducted to evaluate the migration and invasion abilities of BCPAP and K1 cells. Results: The results showed that CASC15 was upregulated in thyroid cancer tissues. Moreover, CASC15 in BCPAP and K1 was decreased by CASC15 siRNA. The progression, migration and invasion of BCPAP cells were significantly decreased after transfection with CASC15 siRNA, which was consistent with that in K1 cells. Furthermore, CASC15 siRNA treatment decreased the level of Bcl-2, and PI3K/AKT, and increased the expression of E-cadherin, BAX, and caspase-3. Conclusions: Downregulated CASC15 inhibited the proliferation, migration and invasion of thyroid cancer. Therefore, CASC15 may be an oncogene in thyroid cancer and may serve as a target marker for the treatment of thyroid cancer.

Reveal the potential molecular mechanism of circRNA regulating immune-related mRNA through sponge miRNA in the occurrence and immune regulation of papillary thyroid cancer.

BACKGROUND: Papillary thyroid cancer (PTC) is the most common endocrine malignant tumour. The purpose of this study was to explore the potential molecular mechanism of circRNA regulating immune-related mRNA through sponge miRNA in the occurrence and immune regulation of PTC. METHODS: All data were downloaded from public databases, such as GEO, Immport and TCGA. Differentially expressed (DE) mRNAs (DEmRNAs), DEmiRNAs and DEcircRNAs were identified using metaMA and limma packages. Subsequently, immune-related DEmRNAs were screened, and circRNA-miRNA-mRNA (ceRNA) regulatory network was constructed. In addition, functional annotation, protein-protein interaction (PPI) network construction, immune cell infiltration analysis and Pearson correlation analysis were performed. Finally, qRT-PCR validation and cell experiments were also performed. RESULTS: In total, 2962 DEmRNAs, 78 DEmiRNAs and 51 DEcircRNAs were obtained. Subsequently, 195 immune-related DEmRNAs were obtained based on Immport database. Cytokine-cytokine receptor interaction was the only signalling pathway obtained in KEGG analysis. Then, 8 hub immune-related DEmRNAs were identified based on PPI network and CytoHubba plug-in. Subsequently, ceRNA sub-network containing hub immune-related DEmRNAs was extracted from ceRNA regulatory network. In ceRNA sub-network, hsa_circ_0082182-hsa-miR-18b-5p-FGF1/PDGFC, hsa_circ_0016404-hsa-miR-1275-FGF1/CTSB/IL13RA1, hsa_circ_0070100-hsa-miR-27a-3p/hsa-miR-27b-3p-TGFBR3, hsa_circ_0060055/hsa_circ_0038718-hsa-miR-150-3p-CXCL14, hsa_circ_0030427/hsa_circ_0002917-hsa-miR-22-3p-BMP7 and hsa_circ_0030427/hsa_circ_0002917-hsa-miR-125a-5p-LIFR axes were identified. Moreover, FGF1, PDGFC, CTSB, IL13RA1, TGFBR3, CXCL14, BMP7, LIFR, hsa-miR-125a-5p, hsa-miR-1275, hsa-miR-150-3p, hsa-miR-18b-5p and hsa-miR-27b-3p were also found to have good diagnostic accuracy and may be potential novel diagnostic markers for PTC. XCell analysis showed that the levels of immune cell infiltration (including Tregs, HSC, DC and Monocytes) were significantly different between the PTC and the control groups. Knockdown of the expression of hsa_circ_0082182 significantly inhibits the activity, proliferation, migration and invasion of TPC-1 cells. CONCLUSION: Several circRNA-miRNA-mRNA axes identified in this study may be related to the occurrence, progression and survival of PTC. This lays a theoretical foundation for further understanding the molecular mechanism of PTC, and also contributes to clinical management and research.

In ceRNA sub-network, hsa_circ_0082182-hsa-miR-18b-5p-FGF1/PDGFC, hsa_circ_0016404-hsa-miR-1275-FGF1/CTSB/IL13RA1, hsa_circ_0070100-hsa-miR-27a-3p/hsa-miR-27b-3p-TGFBR3, hsa_circ_0060055/hsa_circ_0038718-hsa-miR-150-3p-CXCL14, hsa_circ_0030427/hsa_circ_0002917-hsa-miR-22-3p-BMP7 and hsa_circ_0030427/hsa_circ_0002917-hsa-miR-125a-5p-LIFR axes were identified.FGF1, PDGFC, CTSB, IL13RA1, TGFBR3, CXCL14, BMP7, LIFR, hsa-miR-125a-5p, hsa-miR-1275, hsa-miR-150-3p, hsa-miR-18b-5p and hsa-miR-27b-3p were also found to have good diagnostic accuracy and may be potential novel diagnostic markers for PTC.Knockdown the expression of hsa_circ_0082182 significantly inhibits the activity, proliferation, migration and invasion of TPC-1 cell.

Deep learning to diagnose Hashimoto's thyroiditis from sonographic images.

Hashimoto's thyroiditis (HT) is the main cause of hypothyroidism. We develop a deep learning model called HTNet for diagnosis of HT by training on 106,513 thyroid ultrasound images from 17,934 patients and test its performance on 5051 patients from 2 datasets of static images and 1 dataset of video data. HTNet achieves an area under the receiver operating curve (AUC) of 0.905 (95% CI: 0.894 to 0.915), 0.888 (0.836-0.939) and 0.895 (0.862-0.927). HTNet exceeds radiologists' performance on accuracy (83.2% versus 79.8%; binomial test, p < 0.001) and sensitivity (82.6% versus 68.1%; p < 0.001). By integrating serologic markers with imaging data, the performance of HTNet was significantly and marginally improved on the video (AUC, 0.949 versus 0.888; DeLong's test, p = 0.004) and static-image (AUC, 0.914 versus 0.901; p = 0.08) testing sets, respectively. HTNet may be helpful as a tool for the management of HT.

EGR1/2 Inhibits Papillary Thyroid Carcinoma Cell Growth by Suppressing the Expression of PTEN and BAX.

Early growth response (EGR) proteins have been reported to be involved in cell growth and apoptosis in a variety of cancer types and could inhibit tumor development. However, the role of EGR1/2 in papillary thyroid carcinoma (PTC) has not been elucidated. The expression pattern of EGR1/2 in adjacent tissues and cancer tissues and the clinical prognosis of EGR1/2 were analyzed by using the samples from TCGA database. The cell viability was detected by MTT assay. Luciferase reporter assay was used to demonstrate the binding of EGR1/2 to the target gene promotor region. Our results showed that EGR1/2 was significantly downregulated in tumor tissues and correlated with poor prognosis. Overexpression of EGR1/2 inhibited proliferation of IHH-4 and BCPAP cells, and knockdown of EGR1/2 showed a reverse effect. Overexpression of EGR1 or EGR2 promoted phosphatase and tension homolog (PTEN) or Bcl-2-associated X (BAX) expression, and EGR1 or EGR2 was able to directly bind to the promoter region of PTEN or BAX. In conclusion, we found that the altered expression of EGR1/2 affected the proliferation of PTC cells and regulated the expression of PTEN and BAX.

1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea Protects the Blood-Brain Barrier Against Ischemic Injury by Upregulating Tight Junction Protein Expression, Mitigating Apoptosis and Inflammation In Vivo and In Vitro Model.

We previously have revealed that 1-trifluoromethoxyphenyl-3-(1- propionylpiperidin-4-yl) urea (TPPU), as a soluble epoxide hydrolase (sEH) inhibitor can reduce infarct volume, protect blood-brain barrier (BBB) and brain against ischemic injury in rats. Here, we investigated the potential mechanisms of TPPU on BBB integrity in both in permanent middle cerebral artery occlusion (pMCAO) rat model and in oxygen-glucose deprivation/reperfusion (OGD/R)-induced human brain microvascular endothelial cells (HBMVECs) model. In pMCAO rat, TPPU administration decreased brain edema and Evans blue content, increased tight junction proteins (TJs) expression of claudin-5, occludin, and zonula occludens-1 (ZO-1). In OGD/R model, OGD/R significantly increased permeability and cell apoptosis, downregulated the expression of claudin-5, ZO-1, occludin, and lymphoma (Bcl)-2. Notably, TPPU pretreatment effectively protected the BBB integrity by reducing the permeability, promoting expression of claudin-5, ZO-1, occluding and Bcl-2, mitigating reactive oxygen species (ROS) injury and release of interleukin-1ß (IL-1ß), IL-6ß, and tumor necrosis factor-α (TNF-α), downregulating expression of matrix metalloproteinase-9 (MMP-9), MMP-2, bcl-2-associated X protein (Bax), IL-1ß, IL-6ß, and TNF-α. Moreover, OGD/R induced the up-regulation of p-p65, p-IκB, and p-p38, which were effectively decreased after TPPU pretreatment in comparison with that of the OGD/R group. Furthermore, pyrrolidinedithiocarbamate (PDTC, a selective inhibitor of NF-κB p65) not only alleviated the OGD/R-induced HBMVECs injury and permeability, but also reduced the expression of TNF-α, IL-6, IL-1ß, p-p65, and p-IκB, and the protective effect of PDTC was equivalent to that of TPPU. These results indicate that TPPU protects BBB integrity against ischemic injury by multiple protective mechanisms, at least in part, by reducing ROS, inflammation, apoptosis, and suppressing the nuclear factor-κB (NF-κB) and p38 signaling pathways.

Combined Treatment With 2-(2-Benzofu-Ranyl)-2-Imidazoline and Recombinant Tissue Plasminogen Activator Protects Blood-Brain Barrier Integrity in a Rat Model of Embolic Middle Cerebral Artery Occlusion.

Recombinant tissue plasminogen activator (rt-PA) is used to treat acute ischemic stroke but is only effective if administered within 4.5 h after stroke onset. Delayed rt-PA treatment causes blood-brain barrier (BBB) disruption and hemorrhagic transformation. The compound 2-(-2-benzofuranyl)-2-imidazoline (2-BFI), a newly discovered antagonist of high-affinity postsynaptic N-methyl-D-aspartate (NMDA) receptors, has been shown to have neuroprotective effects in ischemia. Here, we investigated whether combining 2-BFI and rt-PA can ameliorate BBB disruption and prolong the therapeutic window in a rat model of embolic middle cerebral artery occlusion (eMCAO). Ischemia was induced in male Sprague Dawley rats by eMCAO, after which they were treated with 2-BFI (3 mg/kg) at 0.5 h in combination with rt-PA (10 mg/kg) at 6 or 8 h. Control rats were treated with saline or 2-BFI or rt-PA. Combined therapy with 2-BFI and rt-PA (6 h) reduced the infarct volume, denatured cell index, BBB permeability, and brain edema. This was associated with increased expression of aquaporin 4 (AQP4) and tight junction proteins (occludin and ZO-1) and downregulation of intercellular adhesion molecule 1 (ICAM-1) and matrix metalloproteinases 2 and 9 (MMP2 and MMP9). We conclude that 2-BFI protects the BBB from damage caused by delayed rt-PA treatment in ischemia. 2-BFI may therefore extend the therapeutic window up to 6 h after stroke onset in rats and may be a promising therapeutic strategy for humans. However, mechanisms to explain the effects oberved in the present study are not yet elucidated.

Erratum: c-Myc-Induced Long Non-Coding RNA Small Nucleolar RNA Host Gene 7 Regulates Glycolysis in Breast Cancer.

[This corrects the article on p. 533 in vol. 22, PMID: 31897328.].

Protective Effects of the Soluble Epoxide Hydrolase Inhibitor 1-Trifluoromethoxyphenyl-3-(1-Propionylpiperidin-4-yl) Urea in a Rat Model of Permanent Middle Cerebral Artery Occlusion.

Acute ischemic stroke is a serious disease that endangers human health. In our efforts to develop an effective therapy, we previously showed that the potent, highly selective inhibitor of soluble epoxide hydrolase called 1-trifuoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) protects the brain against focal ischemia in rats. Here we explored the mechanism of TPPU action by assessing whether it could preserve blood-brain barrier integrity and reduce apoptosis in the brain during permanent middle cerebral artery occlusion in male Sprague-Dawley rats. TPPU administration at the onset of stroke and once daily thereafter led to smaller infarct volume and brain edema as well as milder neurological deficits. TPPU significantly inhibited the activity of soluble epoxide hydrolase and matrix metalloproteases 2 and 9, reducing 14,15-DHET levels, while increasing expression of tight junction proteins. TPPU decreased numbers of apoptotic cells by down-regulating the pro-apoptotic proteins BAX and Caspase-3, while up-regulating the anti-apoptotic protein BCL-2. Our results suggest that TPPU can protect the blood-brain barrier and reduce the apoptosis of brain tissue caused by ischemia.

Aflatoxin B1 impairs leydig cells through inhibiting AMPK/mTOR-mediated autophagy flux pathway.

Aflatoxin B1 (AFB1), a potential endocrine disrupter, has been shown to induce hepatotoxicity in animal models, but the effects of AFB1 on Leydig cell function are unclear. In this study, in vivo exposure to AFB1 at 15 and 150 µg/kg/day lowered serum testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) levels, reduced Leydig cell number, and down-regulated the expression of testosterone biosynthesis-related genes. In vitro study showed that AFB1 (10 µM) significantly increased ROS levels, and decreased T production in Leydig cells by suppressing certain T-biosynthesis gene expressions. Moreover, AFB1 induced Leydig cell apoptosis through lowering pAMPK/AMPK ratio and increasing pmTOR/mTOR ratio, and then further up-regulating autophagy and apoptosis proteins, LC3, BECLIN 1, and BAX, as well as down-regulating autophagy flux protein P62 and anti-apoptosis protein BCL-2. AFB1-induced toxicity in Leydig cells was characterized by inhibiting T-biosynthesis gene expression, reducing Leydig cell number, promoting ROS production, and inducing cell apoptosis via suppressing AMPK/mTOR-mediated autophagy flux pathway.

c-Myc-Induced Long Non-Coding RNA Small Nucleolar RNA Host Gene 7 Regulates Glycolysis in Breast Cancer.

PURPOSE: Recent studies have shown that long non-coding RNA (lncRNA) play an important role in cancer metabolism and development. The lncRNA small nucleolar RNA host gene 7 (SNHG7) was reported to be upregulated in colorectal cancer and contribute to its progression. In the current study, we investigated the role of lncRNA-SNHG7 in breast cancer and explored the underlying mechanism. METHODS: We monitored the expression of lncRNA-SNHG7 in breast cancer tissues and breast cancer cell lines. We evaluated the effects of lncRNA-SNHG7 on cell proliferation and glycolysis in breast cancer cells by knocking down or overexpressing lncRNA-SNHG7. We searched for the potential microRNA (miRNA) target of lncRNA-SNHG7 and evaluated the effects of the target miRNA on glycolysis. We evaluated the potential regulation of lncRNA-SNHG7 by c-Myc. RESULTS: LncRNA-SNHG7 was up-regulated in both breast cancer tissues and breast cancer cell lines. Knocking down lncRNA-SNHG7 inhibited breast cancer cell proliferation while overexpressing lncRNA-SNHG7 enhanced cell proliferation. Knocking down lncRNA-SNHG7 resulted in decreased expression of lactate dehydrogenase A (LDHA) and decreased glycolysis. LncRNA-SNHG7 targeted miR-34a-5p to regulate LDHA expression and glycolysis. c-Myc bound to promoter of lncRNA-SNHG7 and positively regulated lncRNA-SNHG7 expression. CONCLUSION: We demonstrated that c-Myc regulated glycolysis through the lncRNA-SNHG7/miR-34a-5p/LDHA axis in breast cancer cells.

2-(2-Benzofuranyl)-2-imidazoline treatment within 5 hours after cerebral ischemia/reperfusion protects the brain.

We previously demonstrated that administering 2-(2-benzofuranyl)-2-imidazolin (2-BFI), an imidazoline I2 receptor agonist, immediately after ischemia onset can protect the brain from ischemic insult. However, immediate administration after stroke is difficult to realize in the clinic. Thus, the therapeutic time window of 2-BFI should be determined. Sprague-Dawley rats provided by Wenzhou Medical University in China received right middle cerebral artery occlusion for 120 minutes, and were treated with 2-BFI (3 mg/kg) through the caudal vein at 0, 1, 3, 5, 7, and 9 hours after reperfusion. Neurological function was assessed using the Longa's method. Infarct volume was measured by 2,3,5-triphenyltetrazolium chloride assay. Morphological changes in the cortical penumbra were observed by hematoxylin-eosin staining under transmission electron microscopy . The apoptosis levels in the ipsilateral cortex were examined with terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) assay. The protein expression of Bcl-2 and BAX was detected using immunohistochemistry. We found the following: Treatment with 2-BFI within 5 hours after reperfusion obviously improved neurological function. Administering 2-BFI within 9 hours after ischemia/reperfusion decreased infarct volume and alleviated apoptosis. 2-BFI administration at different time points after reperfusion alleviated the pathological damage of the ischemic penumbra and reduced the number of apoptotic neurons, but the protective effect was more obvious when administered within 5 hours. Administration of 2-BFI within 5 hours after reperfusion remarkably increased Bcl-2 expression and decreased BAX expression. To conclude, 2-BFI shows potent neuroprotective effects when administered within 5 hours after reperfusion, seemingly by up-regulating Bcl-2 and down-regulating BAX expression. The time window provided clinical potential for ischemic stroke by 2-BFI.

Protective effects of 2-(2-benzonfuranyl)-2-imidazoline combined with tissue plasminogen activator after embolic stroke in rats.

Stroke is the third leading cause of death and disability in developing countries. The effective therapy for acute ischemic stroke is thrombolysis with recombinant tissue plasminogen activator (rt-PA) within 4.5 h of stroke onset. An effective post-ischemic neuroprotectant would extend the advantages of rt-PA, and protect against complications of thrombolysis. We previously reported that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a newly discovered ligand for high-affinity type 2 imidazoline receptor (I2R), provides neuroprotection against ischemic stroke in rats. Here we investigated the protective effects of 2-BFI in combination with delayed intravenous rt-PA after stroke induced by embolic middle cerebral artery occlusion (eMCAO) in rats. Infarct size was determined using 2,3,5-triphenyltrazolium chloride staining, while neurological deficit was assessed based on neurological score. Numbers of apoptotic cells in vivo were estimated using TUNEL stain, and expression of the pro-apoptotic protein BAX and anti-apoptotic protein BCL-2 were quantified by Western blotting. The results showed that 2-BFI (3 mg/kg) administered at 0.5 h after embolic MCAO combined with rt-PA (10 mg/kg) administered at 6 h reduced brain infarct size, mitigated neurological deficit, decreased the number of TUNEL-positive cells, down-regulated BAX expression, and up-regulated BCL-2 expression. These findings suggest that 2-BFI may extend the therapeutic window of rt-PA to 6 h after embolic stroke onset in rats.

Effects of Therapeutic Hypothermia Combined with Other Neuroprotective Strategies on Ischemic Stroke: Review of Evidence.

Ischemic stroke is a major cause of death and disability globally, and its incidence is increasing. The only treatment approved by the US Food and Drug Administration for acute ischemic stroke is thrombolytic treatment with recombinant tissue plasminogen activator. As an alternative, therapeutic hypothermia has shown excellent potential in preclinical and small clinical studies, but it has largely failed in large clinical studies. This has led clinicians to explore the combination of therapeutic hypothermia with other neuroprotective strategies. This review examines preclinical and clinical progress towards developing highly effective combination therapy involving hypothermia for stroke patients.

2-(2-Benzofuranyl)-2-Imidazoline Mediates Neuroprotection by Regulating the Neurovascular Unit Integrity in a Rat Model of Focal Cerebral Ischemia.

BACKGROUND: We showed previously that 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a ligand to type 2 imidazoline receptor (I2R) exerts neuroprotective effects in ischemia stroke via an unknown mechanism. The present study was to investigate whether 2-BFI can protect the neurovascular unit (NVU) using a rat model of 90 min focal cerebral ischemia. METHODS: Rats were randomly divided into three groups: thesham-operated group; the vehicle control group and the 2-BFI group which received 2-BFI (3 mg/kg) immediately after the start of middle cerebralartery occlusion (MCAO). Neurological deficit score, infarct size, apoptosis level, brain water content and Evans Blue extravasation were assessed at 24 h after stroke. Expressions of occludin and zonula occludens 1 (ZO-1), collagen IV, aquaporin-4 (AQP-4), matrix metalloproteinase-9 (MMP-9) and MMP-2 were assessed by Western blotting. RESULTS: 2-BFI treatment was associated with significant improvement of neurological performance and decreased infarct volume at 24 h after stroke. Apoptosis level reduced significantly by 2-BFI compared to the vehicle group (34.3 ± 5.4% vs 56.1 ± 7.9%, p < 0.05). Significant decreased of brain water content (79.5 ± 2.6% vs 84.62 ± 2%, p < 0.05) and Evans Blue extravasation (1.2 ± 0.5 vs 2.5 ± 0.41 µg/g, p < 0.05) of ipsilateral hemisphere was observed in 2-BFI group compared to vehicle group. Expressions of occludin, ZO-1 and collagen IV were significantly higher while MMP-9 level significantly lower in 2-BFI group. AQP-4 and MMP-2 showed no difference between 2-BFI and the vehicle groups. CONCLUSIONS: These results suggest that the neuroprotective effects of 2-BFI in acute ischemic brain damage are at least partly due to the drug's ability to improve the functions of NVU.

The lncRNA n340790 accelerates carcinogenesis of thyroid cancer by regulating miR-1254.

Long non-coding RNAs (lncRNAs) have been recently reported to be dysregulated and play a critical role in the progression of thyroid cancer. Here, we found that the lncRNA n340790 was highly expressed in human thyroid cancer tissues and was strongly correlated with the clinical characteristics of patients. There was a good prognostic value of n340790 for thyroid cancer. In vitro overexpression of n340790 promoted the development of thyroid cancer, while silencing n340790 inhibited this process. Additionally, n340790 accelerated the growth of thyroid cancer tumor in vivo. Furthermore, we discovered that n340790 could act as an endogenous sponge by directly binding to miR-1254 and downregulating miR-1254 expression. In addition, miR-1254 could inhibit the stimulatory effect of n340790 on the growth and invasion of thyroid cancer cells. In conclusion, n340790 promoted the development process of malignant thyroid cancer by regulating miR-1254, and targeting n340790 may be a promising strategy as a thyroid cancer therapy.

Association Studies Between XRCC1, XRCC2, XRCC3 Polymorphisms and Differentiated Thyroid Carcinoma.

BACKGROUND/AIMS: DNA HRR pathway and BER pathway play vital roles in differentiated thyroid cancer (DTC) development, thus we supposed that polymorphisms of XRCC1, XRCC2, XRCC3 DNA repair genes are associated with thyroid cancer risk and progression. METHODS: We searched the NCBI database for relevant literatures to determine eight SNPs to be included in our study (XRCC1: rs25487, rs25489, rs1799782; XRCC2: rs3218536; XRCC3: rs1799794, rs56377012, rs1799796, rs861539). RESULTS: SNP of rs25487 was linked with a 53% decrease in DTC risk (OR: 0.47; 95%CI: 0.268-0.82; P = 0.01). For SNP of rs1799782, the homozygous TT genotype indicated a statistically significant 2-fold increased risk of DTC (OR: 2.09; 95%CI: 1.27-3.43; P < 0.001) after multivariate adjustment. For SNP of rs861539, the homozygous TT genotype suggested statistically significant 3-fold increased risk of DTC (OR: 3.02; 95%CI: 1.68-5.42; P < 0.001). No significant association between the other five SNPs and DTC risk. Besides that, female was linked with 47% increase in DTC risk (OR: 1.47; 95%CI: 1.062-2.04; P = 0.02) after multivariate adjustment. Similar results for most of the SNPs were obtained from subgroup analysis by different histological types of DTC. Haplotype analysis revealed that AGC and GGT haplotypes of XRCC1 polymorphisms were associated with DTC. Moreover, results from gene-gene interaction showed that XRCC1-rs25487, XRCC1- rs1799782 and XRCC3- rs861539 variants jointly contributed to a specifically increased risk of DTC, with the combination variant of rs1799782-CT heterozygote and rs861539-TT homozygote exhibiting a higher 3.66-fold risk of DTC (OR: 3.66; 95% CI: 1.476-9.091, P = 0.005). CONCLUSION: Polymorphisms of XRCC1 (rs25487, rs1799782) and XRCC3 (rs861539), may play a critical role in DTC development and progression. Furthermore, XRCC1 variant can interact with XRCC3 variant to significantly increase DTC susceptibility. Identifying these genetic risk markers could provide evidence for exploring the insight pathogenesis and develop novel therapeutic strategies for DTC.

Expression of signal transducer and activator of transcription 3 and its phosphorylated form is significantly upregulated in patients with papillary thyroid cancer.

The aim of the present study was to investigate the expression of signal transducer and activator of transcription 3 (STAT3) and phosphorylated STAT3 (pSTAT3) in tissues of papillary thyroid cancer (PTC) in comparison with the expression in adjacent normal tissues. The expression of STAT3, pSTAT3, fibroblast growth factor 2 (FGF2) and vascular endothelial growth factor-C (VEGF-C) was examined in tissues of 42 cases of PTC and the adjacent normal tissues of 20 of the 42 PTC cases using immunohistochemistry and western blotting. The association between the expression levels and the clinicopathological features was analyzed. The expression of STAT3, pSTAT3, FGF2 and VEGF-C in the PTC tissues (76.2, 42.9, 81.0 and 73.8%, respectively) was significantly higher than that in the normal tissues (P<0.05). In the PTC tissues, the expression of STAT3 was linearly correlated with the levels of pSTAT3 and VEGF-C (P<0.05). In conclusion, STAT3 and pSTAT3 are significantly upregulated in PTC tissues, and may potentially be used as markers to screen for PTC with lymph node metastasis.

[Expression of thyroid stimulating hormone receptor in differentiated thyroid carcinoma and its clinical significance].

OBJECTIVE: To explore the expression of thyroid stimulating hormone (TSH) receptor in differentiated thyroid carcinoma and its clinical significance. METHODS: Seventy-four patients with differentiated thyroid carcinoma treated in our department from January 2009 to January 2011 were selected as the observation group, and 28 patients with nodular goiter were selected as the control group. Expression of TSH receptor in the two groups were detected by immunohistochemistry. RESULTS: The positive rate of TSH receptor expression in the observation group was 55.4 (41/74), significantly lower than that of the control group (89.3%, 25/28), with a significant difference between the two groups (χ(2) = 10.21, P < 0.05). In the observation group, the positive rate of TSH receptor expression was 75.9% (22/29) in the stage I patients, 47.8% (11/23) in the stage II patients, 38.9%6 (7/18) in the stage III patients, and 25.0% (1/4) in the stage IV patients. Along with the increase of TNM staging, the positive rate of TSH receptor expression was decreased gradually, with a significant difference between them (χ(2) = 8.93, P < 0.05). The positive rate of TSH receptor expression was 53.8% (14/26) in the lymph node metastasis positive group and 56.3% (27/48) in the lymph node metastasis negative groups, with a non-significant difference between them (χ(2) = 0.04, P > 0.05). CONCLUSIONS: Expression of TSH receptors in the patients with differentiated thyroid carcinoma is quite low, and along with the increase of TNM staging, its positive rate is decreasing gradually. Testing the expression of TSH receptor may provide a basis for TSH suppression therapy after thyroid cancer surgery. This TSH suppression therapy should be personalized in order to reduce the side effects and improve their quality of life.