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Objective To explore the effect of KCNQ1OT1 gene knockout combined with bruceine D on the proliferation, migration, and invasion of breast cancer MDA-MB-231 cells. Methods Cell Counting Kit-8, wound healing, and Transwell invasion assay were used to detect the effects of bruceine D and siKCNQ1OT1 on the viability, migration, and invasion of MDA-MB-231 cells. Effect of bruceine D and siKCNQ1OT1 on the expression of KCNQ1OT1 in MDA-MB-231 cells was detected by qRT-PCR. Western blot was used to detect the effect of bruceine D and siKCNQ1OT1 on the expression of EMT-related proteins and CDC42, p-MKK7, MKK7 proteins in MDA-MB-231 cells. Results Bruceine D and siKCNQ1OT1 could significantly inhibit the viability, migration, and invasion of MDA-MB-231 cells, and the inhibitory effect was enhanced when they were combined (all P < 0.05); bruceine D downregulated the expression of KCNQ1OT1 in MDA-MB-231 cells (all P < 0.05); bruceine D combined with siKCNQ1OT1 significantly decreased CDC42, p-MKK7, N-cadherin, and Vimentin expression in MDA-MB-231 cells and increased the expression of E-cadherin (all P < 0.05). Conclusion Bruceine D combined with siKCNQ1OT1 significantly inhibit the proliferation, migration, invasion, and EMT of human breast cancer MDA-MB-231 cells, and its molecular mechanism may be related to the blocking of CDC42/MKK7 signaling pathway.
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Objective:To explore the inhibitory effect of long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) by targeting microRNA-199a-5p (miR-199a-5p) on the apoptosis of human lens epithelial cells (LECs).Methods:The anterior lens capsule tissue of 23 age-related cataract patients who underwent cataract surgery in Xinxiang First People's Hospital from December 2018 to August 2019 was collected.At the same time, anterior lens capsules from 20 healthy donor were collected.The expressions of KCNQ1OT1 and miR-199a-5p in the tissues were detected by real-time fluorescence PCR.Human LECs SRA01/04 cultured in vitro were divided into blank control group, model control group, small interfering RNA-negative control (siR-NC) group, siR-KCNQ1OT1 group, miR-NC group, miR-199a-5p group, siR-KCNQ1OT1+ anti-miR-NC group and siR-KCNQ1OT1+ anti-miR-199a-5p group.No intervention was administered to blank control group.Cells in model control group were cultured with 100 μmol/L H 2O 2 for 24 hours to establish oxidative stress injured model, and cells in the other six groups were transfected with corresponding transfection reagents for 6 hours by liposome method according to grouping, and then treated with 100 μmol/L H 2O 2 for 24 hours.The expressions of KCNQ1OT1 and miR-199a-5p in lens anterior capsule tissue and LECs cells were determined by real-time fluorescent quantitative PCR.Cell viability was detected with thiazolyl blue (MTT). Cell apoptosis was analyzed by flow cytometry.The expressions of B-cell lymphoma/leukemia-2 (bcl-2) and bcl-2 related X protein (Bax) proteins were assayed by Western blot.The superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by enzyme-linked immunosorbent assay (ELISA). The targeting relationship between KCNQ1OT1 and miR-199a-5p was verified by dual luciferase reporter experiment.The study protocol was approved by an Ethics Committee of Xinxiang First People's Hospital (No.2019-001). Written informed consent was obtained from relatives of patient. Results:The relative expression of KCNQ1OT1 in the anterior capsule of patients with age-related cataract was 2.41±0.42, which was significantly higher than 0.97±0.19 of normal people, and the relative expression of miR-199a-5p in the capsule of patients with age-related cataract was 0.36±0.12, which was lower than 1.04±0.15 of normal people, and the differences were statistically significant ( t=14.112, 16.507; both at P<0.001). Compared with blank control group, the relative expressions of KCNQ1OT1 and bax protein, cell apoptosis rate and MDA content were significantly increased, and the relative expressions of miR-199a-5p and bcl-2 protein, cell viability and SOD activity were significantly reduced in model control group, showing statistically significant differences (all at P<0.001). Compared with siR-NC group, the relative expressions of KCNQ1OT1 and bax protein, cell apoptosis rate and MDA content in cells of siR-KCNQ1OT1 group were decreased, while the relative expression of bcl-2 protein, cell survival rate and SOD activity were increased, and the differences were statistically significant (all at P<0.05). Compared with miR-NC group, the KCNQ1OT1-wild type (WT) luciferase activity in miR-199a-5p group was significantly decreased, with a statistically significant difference ( t=21.131, P<0.001). The relative expression levels of miR-199a-5p and bcl-2 proteins, cell survival rate and SOD activity were significantly increased, and the relative expression of bax protein, cell apoptosis rate and MDA content were significantly decreased in miR-199a-5p group than those in miR-NC group, and the differences were statistically significant (all at P<0.05). The relative expression levels of miR-199a-5p and bcl-2 proteins, cell survival rate and SOD activity were significantly lower, and the cell apoptosis rate, relative expression of bax protein and MDA content were significantly higher in siR-KCNQ1OT1+ anti-miR-199a-5p group than those in siR-KCNQ1OT1+ anti-miR-NC group, and the differences were statistically significant (all at P<0.05). Conclusions:The inhibition of KCNQ1OT1 can promote the cell viability of human LECs, inhibit H 2O 2-induced cell apoptosis and oxidative stress, and the mechanism may be related to the up-regulation of miR-199a-5p.
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Long non-coding RNA KCNQ1OT1 is highly expressed in a variety of tumors, but there are few studies in gastric cancer and the results are inconsistent. The relevant research of its specific mechanism in gastric cancer is also scarce. Through the analysis of several TCGA public databases, we found that KCNQ1OT1 was generally highly expressed in gastric cancer, and the prognosis of gastric cancer patients with a high expression of KCNQ1OT1 was poor. The expression of KCNQ1OT1 is closely related to many clinical factors of gastric cancer, especially the mutation of TP53, and its expression is significantly related to immune cell infiltration. KCNQ1OT1 is generally highly expressed in gastric cancer cell lines. Knockdown of KCNQ1OT1 can inhibit the proliferation of gastric cancer cell lines. Co- expression network analysis showed that its expression was closely related to tumor metabolism. Glutaminase 1 (GLS1) is generally highly expressed in gastric cancer, which is closely related to a poor prognosis. There is a significant correlation between the expression of KCNQ1OT1 and GLS1. Knockdown of KCNQ1OT1 can inhibit the expression of GLS1 mRNA, and overexpression of GLS1 can partially rescue the proliferation of gastric cancer cells caused by knockdown of KCNQ1OT1. Therefore, we speculate that KCNQ1OT1 may regulate the growth of gastric cancer cells through GLS1. Our study explored the role of KCNQ1OT1 in gastric cancer through bioinformatics database and experiments, suggesting that KCNQ1OT1 may promote the development of gastric cancer by regulating glutamine metabolism, which provides a new target for the clinical research on targeted treatment in gastric cancer.
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@#AIM: To investigate whether long-chain non-coding RNA(lncRNA)KCNQ1OT1 affects the proliferation, apoptosis and oxidative stress of retinal epithelial cells induced by high glucose(HG)through miR-19a-3p/TSHZ3. <p>METHODS: Cell counting kit 8(CCK-8)was used to detect the cell viability of human retinal epithelial cells ARPE-19 stimulated with 5, 15, 45, 135mmol/L HG. The ARPE-19 cells were divided into NC group, 45mmol/L HG group, si-NC+45mmol/L HG group, si-lncRNA KCNQ1OT1+45mmol/L HG group, miR-NC+45mmol/L HG group, miR-19a-3p mimics+45mmol/L HG group, si-con+45mmol/L HG group, si-TSHZ3+45mmol/L HG group, pcDNA+si-lncRNA KCNQ1OT1+45mmol/L HG group, pcDNA-TSHZ3+si-lncRNA KCNQ1OT1+45mmol/L HG group. CCK-8 was used to detect cell viability, qRT-PCR was used to detect the expressions of lncRNA KCNQ1OT1, miR-19a-3p and TSHZ3 mRNA, Western Blot was used to detect TSHZ3, activation-cysteine-containing aspartate proteolytic enzyme 3(Cleaved-caspase-3), B-cell lymphoma/leukemia-2(Bcl-2)related X protein(Bax)protein expressions, and enzyme-linked immunosorbent assay(ELISA)was used to detect the levels of oxidative stress indicators reactive oxygen species(ROS)and malondialdehyde(MDA). The dual luciferase activity was used to detect the targeted binding between lncRNA KCNQ1OT1 and miR-19a-3p, miR-19a-3p and TSHZ3. <p>RESULTS: 15, 45, 135mmol/L HG inhibited the survival rate of ARPE-19 cells, and the subsequent select the HG concentration 45mmol/L with a cell survival rate of about 50%. 45mmol/L HG increased the expression levels of lncRNA KCNQ1OT1, TSHZ3 mRNA, TSHZ3 protein, the apoptosis rate, Cleaved-caspase-3 and Bax protein expressions, ROS and MDA levels in ARPE-19 cells, and reduced cell survival rate and the expression level of miR-19a-3p(<i>P</i><0.05). Low expression of lncRNA KCNQ1OT1, TSHZ3 or high expression of miR-19a-3p improved the survival rate of ARPE-19 cells induced by HG, and reduced apoptosis rate, Cleaved-caspase-3 and Bax protein expressions, ROS and MDA levels(<i>P</i><0.05). lncRNA KCNQ1OT1 targeted miR-19a-3p, miR-19a-3p targeted TSHZ3, and lncRNA KCNQ1OT13 regulated the expression of TSHZ3 through miR-19a-3p. The effect of lncRNA KCNQ1OT1 low expression on the survival rate, apoptosis and oxidative stress of ARPE-19 cells induced by HG was reversed by the overexpression of TSHZ3.<p>CONCLUSION: The low expression of lncRNA KCNQ1OT13 promotes the proliferation of retinal epithelial cells induced by high glucose, and inhibits their apoptosis and oxidative stress through miR-19a-3p/TSHZ3.
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OBJECTIVE@#To investigate the regulatory role of long non-coding RNA Kcnq1ot1 in osteoclast differentiation, osteogenic differentiation and osteoporosis.@*METHODS@#The expression of lnc-Kcnq1ot1, Bglap, Runx2, Alp, Bsp, Nfatc1, Mmp9, Ctsk and Oscar were detected by real-time quantitative PCR (qRT-PCR) in the femoral bones from mouse models of postmenopausal osteoporosis (ovariectomized mice, @*RESULTS@#The expression of lnc-Kcnq1ot1 was significantly upregulated during osteoblast differentiation but downregulated in the bone tissues of osteoporotic mice and during osteoclast differentiation (@*CONCLUSIONS@#Our data demonstrate that lnc-Kcnq1ot1 promotes osteogenic differentiation and alleviates osteoclast differentiation, suggesting the potential of lnc-Kcnq1ot1 as a therapeutic target against osteoporosis.
الموضوعات
Animals , Mice , Cell Differentiation , Cells, Cultured , Osteoblasts , Osteoclasts , Osteogenesisالملخص
@#Objective To detect the expression of PITX2 and KCNQ1 in the left atrial appendage of patients with atrial fibrillation after modified mini-maze procedure, and to detect the clinical risk factors of different types of atrial fibrillation. Methods We collected left atrial appendage tissue of 59 atrial fibrillation patients who received modified mini-maze procedure and left atrial appendectomy from February 2017 to August 2018. The expression levels of PITX2 and KCNQ1 of left atrial appendage tissue were quantitatively analyzed by western blotting assay between paroxysmal attial fibrillation and persistent atrial fibrillation groups. The correlation between protein expression and prognosis after surgery was also analyzed based on clinical data. Results Binary-logistic regression analysis showed that KCNQ1 expression level was an independent risk factor for the progression from paroxysmal atrial fibrillation to persistent atrial fibrillation. Receiver operating characteristic (ROC) curve confirmed that KCNQ1 expression level (the ratio of KCNQ1 to actin in the analysis) was 0.60, which was the best cut-off point for the progression of paroxysmal atrial fibrillation to persistent atrial fibrillation. Conclusion High expression of KCNQ1 in left atrial appendage is a risk factor for progression from paroxysmal atrial fibrillation to persistent atrial fibrillation.
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Mesocorticolimbic dopaminergic (DA) neurons have been implicated in regulating nociception in chronic pain, yet the mechanisms are barely understood. Here, we found that chronic constructive injury (CCI) in mice increased the firing activity and decreased the KCNQ channel-mediated M-currents in ventral tegmental area (VTA) DA neurons projecting to the nucleus accumbens (NAc). Chemogenetic inhibition of the VTA-to-NAc DA neurons alleviated CCI-induced thermal nociception. Opposite changes in the firing activity and M-currents were recorded in VTA DA neurons projecting to the medial prefrontal cortex (mPFC) but did not affect nociception. In addition, intra-VTA injection of retigabine, a KCNQ opener, while reversing the changes of the VTA-to-NAc DA neurons, alleviated CCI-induced nociception, and this was abolished by injecting exogenous BDNF into the NAc. Taken together, these findings highlight a vital role of KCNQ channel-mediated modulation of mesolimbic DA activity in regulating thermal nociception in the chronic pain state.
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Dendrobium nobile Lindl. alkaloids (DNLA) promote the apoptosis of breast cancer and colon cancer cells, but whether they affect the malignant biological behavior of cervical cancer cells is unknown. Herein we explored the effects and possible mechanisms of DNLA on the proliferation, apoptosis, migration and invasion of cervical cancer SiHa cells. SiHa cells were transfected with si-NC, siKCNQ1OT1, miR-NC, miR-487a-3p mimics, pcDNA-NC or pcDNA-KCNQ1OT1. Different doses (15, 30, 60 ng/mL) of DNLA were applied. The CCK-8 method was used to detect cell proliferation; Tran-swell was used to detect cell migration and invasion; flow cytometry was used to detect cell apoptosis; Western blotting was used to detect the expression of MMP2, MMP9 and Cleaved-Caspase-3 genes at the protein level; RT-qPCR was used to detect the expression of KCNQ1OT1 and miR-487a-3p. The dual luciferase reporter gene experiment verified the regulatory relationship between KCNQ1OT1 and miR-487a-3p. The results showed that different doses (15, 30, 60 ng/mL) of DNLA reduced the absorbance value, migration number, invasion number, the protein level of MMP2 and MMP9, reduced the expression of KCNQ1OT1, and increased the apoptosis rate, the abundance of Cleaved-Caspase-3 and the expression of miR-487a-3p (P<0. 05). Low expression of KCNQ1OT1 or high expression of miR-487a-3p reduced the absorbance value, migration number, invasion number, and the protein level of MMP2 and MMP9, but increased the apoptosis rate and the abundance of Cleaved-Caspase-3 (P<0. 05). KCNQ1OT1 negatively regulated the expression of miR-487a-3p. The effects of high expression of KCNQ1OT1 on the proliferation, apoptosis, migration and invasion of SiHa cells were opposite to that of low expression of KCNQ1OT1, and high expression of KCNQ1OT1 reduced the effects of 60 ng/mL DNLA on the proliferation, apoptosis, migration and invasion of SiHa cells. In summary, DNLA may reduce the proliferation, migration and invasion of cervical cancer SiHa cells and promote SiHa cell apoptosis by regulating the KCNQ1OT1/miR-487a-3p axis.
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Sevoflurane (SEVO) is widely applied as an anesthetic, which exerts antitumor capacity in various cancers, including hepatocellular carcinoma (HCC). Previous studies indicated that long non-coding RNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1) was upregulated, while microRNA-29a-3p (miR-29a-3p) was downregulated in HCC. Thus, we aimed to explore the roles of KCNQ1OT1 and miR-29a-3p in HCC cells exposed to SEVO. Cell proliferation, apoptosis, migration, and invasion were assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, and transwell assays, respectively. The levels of genes were determined by quantitative real-time polymerase chain reaction (qRT-PCR) or western blot. Furthermore, the interaction between miR-29a-3p and KCNQ1OT1 or chromebox protein homolog 3 (CBX3) was predicted by Starbase or Targetscan, and then confirmed by dual-luciferase reporter assay. We found that the levels of KCNQ1OT1 and CBX3 were decreased, while miR-29a-3p was increased in SEVO-treated HCC cells. KCNQ1OT1 overexpression weakened the inhibitory effects of SEVO on HCC cell proliferation, apoptosis, migration, and invasion. Interestingly, KCNQ1OT1 bound to miR-29a-3p, and miR-29a-3p targeted CBX3. KCNQ1OT1 upregulated CBX3 level by repressing miR-29a-3p expression. Furthermore, KCNQ1OT1 exerted tumor promotion in HCC cells via suppressing miR-29a-3p to regulate CBX3 expression. Collectively, our findings demonstrated that KCNQ1OT1 regulated the antitumor effects of SEVO on HCC cells through modulating the miR-29a-3p/CBX3 axis, providing a theoretical basis for the treatment of HCC.
الموضوعات
Humans , Carcinoma, Hepatocellular/genetics , Carcinoma, Hepatocellular/drug therapy , Potassium Channels, Voltage-Gated , MicroRNAs/genetics , Liver Neoplasms/genetics , Liver Neoplasms/drug therapy , Chromosomal Proteins, Non-Histone , RNA, Long Noncoding/genetics , Sevoflurane/pharmacologyالملخص
OBJECTIVE: The long non-coding RNA (lncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) exerts vital regulatory functions in diverse tumors. However, the biological function of KCNQ1OT1 in esophageal squamous cell carcinoma (ESCC) remains unclear. METHODS: KCNQ1OT1 expression was detected in ESCC tissues using quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation, apoptosis, migration, and invasion were detected by the CCK-8 assay, EdU assay, flow cytometry analysis, and Transwell experiments, respectively. Bioinformatics analysis, luciferase reporter experiments, and RNA immunoprecipitation assays were used to predict and validate the regulatory relationships between KCNQ1OT1, microRNA-133b (miR-133b) and epidermal growth factor receptor (EGFR). RESULTS: KCNQ1OT1 expression was remarkably upregulated in ESCC tissues and cell lines. Overexpression of KCNQ1OT1 markedly promoted ESCC cell proliferation, migration, and invasion and enhanced the expression of N-cadherin, MMP-2, and MMP-9, but inhibited apoptosis and E-cadherin expression in ESCC cell lines; KCNQ1OT1 knockdown exerted the opposite effects. KCNQ1OT1 could directly bind to miR-133b and suppress its expression, and miR-133b reversed the effects of KCNQ1OT1 overexpression in ESCC cells. MiR-133b reduced the expression of epidermal growth factor receptor (EGFR); further, KCNQ1OT1 activated the phosphatidylinositol 3-kinase/AKT serine/threonine kinase 1 (PI3K/AKT) signaling pathway by repressing miR-133b repression and indirectly upregulating EGFR. KCNQ1OT1 expression was positively correlated with EGFR mRNA expression and negatively correlated with miR-133b expression. CONCLUSION: KCNQ1OT1 facilitates ESCC progression by sponging miR-133b and activating the EGFR/PI3K/AKT pathway.
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Humans , Esophageal Neoplasms/genetics , MicroRNAs/genetics , RNA, Long Noncoding/genetics , Esophageal Squamous Cell Carcinoma/genetics , Phosphatidylinositol 3-Kinases , Cell Proliferation/genetics , KCNQ1 Potassium Channel/geneticsالملخص
Abstract Background: Osteoarthritis (OA) is defined as a degenerative disease. Pivotal roles of long non-coding RNA (lncRNAs) in OA are widely elucidated. Herein, we intend to explore the function and molecular mechanism of lncRNA KCNQ1OT1 in CHON-001 cells. Methods: Relative expression of KCNQ1OT1, miR-126-5p and TRPS1 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Cell viability was examined by MTT assay. The migratory ability of chondrocytes was assessed by transwell assay. Western blot was used to determine relative protein expression of collagen II, MMP13 and TRPS1. Dual-luciferase reporter (DLR) assay was applied to test the target of lncRNA KCNQ1OT1 or miR-126-5p. Results: Relative expression of KCNQ1OT1 and TRPS1 was reduced, whereas miR-126-5p was augmented in cartilage tissues of post-traumatic OA patients compared to those of subjects without post-traumatic OA. Increased KCNQ1OT1 or decreased miR-126-5p enhanced cell viability and migration, and repressed extracellular matrix (ECM) degradation in CHON-001 cells. MiR-126-5p was the downstream target of KCNQ1OT1, and it could directly target TRPS1. There was an inverse correlation between KCNQ1OT1 and miR-126-5p or between miR-126-5p and TRPS1. Meantime, there was a positive correlation between KCNQ1OT1 and TRPS1. The promoting impacts of KCNQ1OT1 on cell viability and migration as well as the suppressive impact of KCNQ1OT1 on ECM degradation were partially abolished by miR-126-5p overexpression or TRPS1 knockdown in CHON-001 cells. Conclusions: Overexpression of KCNQ1OT1 attenuates the development of OA by sponging miR-126-5p to target TRPS1. Our findings may provide a possible therapeutic strategy for human OA in clinic.
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Seven indole alkaloid glycosides containing a 1'-(4″-hydroxy-3″,5″-dimethoxyphenyl)ethyl unit (-) were isolated from an aqueous extract of leaves (da qing ye). Their structures were determined by spectroscopic data analysis combined with enzymatic hydrolysis as well as comparison of their experimental CD (circular dichroism) and calculated ECD (electrostatic circular dichroism) spectra. Based on analysis of and/or Cotton effect (CE) data of -, two simple roles to assign location and/or configuration of -glycopyranosyloxy and 1'-(phenyl)ethyl units in the indole alkaloid glycosides are proposed. Stereoselectivity in plausible biosynthetic pathways of - is discussed. Compounds and and their mixture in a 3:2 ratio showed activity against KCNQ2 in CHO cells. The mixture of and (3:2) exhibited antiviral activity against influenza virus H1N1 PR8 with IC 64.7 μmol/L (ribavirin, IC 54.3 μmol/L), however, the individual or was inactive. Preliminary structure-activity relationships were observed.
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Objective@#To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation.@*Methods@#Twenty-two patients were collected in the Department of Pediatrics, Peking University First Hospital from April 2007 to July 2016.The phenotype-genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 mutation was identified by the targeted next generation sequencing.@*Results@#Twenty-two de novo KCNQ2 missense mutations from 22 patients with neonatal/infantile epileptic disorders were found.These patients had an onset of epilepsy in early infancy (median age: 2 days). The seizure type of the first onset was mainly focal seizure.Atypical absence epilepsy, a novel phenotype of KCNQ2 mutation-induced epilepsies was found.The mortality of these patients was high, as 5 patients of the 22 patients died in the follow-up period, 4 of which might result from sudden unexpected death in epilepsy.In the 22 patients, 8 patients with anti-epileptic monotherapy became seizure-free.Of the 8 patients with a monotherapy, 3 patients were treated with valproic acid and no clinical onset was observed.@*Conclusions@#This study expands the phenotype of KCNQ2-related epileptic disorders.These patients have high mortality.Valproate acid is the potentially effective monotherapy for these patients.
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Objective: To investigate the expression of long non-coding RNA (LncRNA) KCNQ1 overlapping transcript 1 (KCNQ1OT1) in the peripheral blood of patients with diffuse large B-cell lymphoma (DLBCL), and to analyze its clinical significance. Methods: The expression of LncRNA KCNQ1OT1 in the serum samples of 120 DLBCL patients and 55 non-tumor patients (as the control group) was detected by real-time fluorescent quantitative PCR. The correlations of LncRNA KCNQ1OT1 expression with the clinicopathological features and prognosis of DLBCL patients were analyzed. Results: The expression level of LncRNA KCNQ1OT1 in the serum of DLBCL patients was higher than that in the control group (P < 0.001). The expression of LncRNA KCNQ1OT1 was correlated with the tumor size, Ann Arbor stage, B symptoms, chemosensitivity and the international prognostic index (IPI) (all P < 0.001). The progression-free survival (PFS) time and the overall survival (OS) time of DLBCL patients with LncRNA KCNQ1OT1 high expression were significantly shorter than those with LncRNA KCNQ1OT1 low expression (both P < 0.001). Ann Arbor stage, LncRNA KCNQ1OT1 expression, IPI and chemosensitivity were the independent prognosis factors for DLBCL patients (all P < 0.01). Conclusion: LncRNA KCNQ1OT1 is highly expressed in the serum of patients with DLBCL, and is one of independent prognosis factors for DLBCL patients.
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Objective To reveal the clinical and genetic features of neonatal/infantile epileptic disorders caused by KCNQ2 mutations and to provide a clue for the treatment and prognosis evaluation. Methods Twenty－two patients were collected in the Department of Pediatrics,Peking University First Hospital from April 2007 to July 2016. The phenotype－genotype analysis was conducted of the neonatal/infantile epileptic patients in whom a KCNQ2 muta﹣tion was identified by the targeted next generation sequencing. Results Twenty－two de noνo KCNQ2 missense muta﹣tions from 22 patients with neonatal/infantile epileptic disorders were found. These patients had an onset of epilepsy in early infancy(median age:2 days). The seizure type of the first onset was mainly focal seizure. Atypical absence epi﹣lepsy,a novel phenotype of KCNQ2 mutation－induced epilepsies was found. The mortality of these patients was high,as 5 patients of the 22 patients died in the follow－up period,4 of which might result from sudden unexpected death in epi﹣lepsy. In the 22 patients,8 patients with anti－epileptic monotherapy became seizure－free. Of the 8 patients with a monotherapy,3 patients were treated with valproic acid and no clinical onset was observed. Conclusions This study expands the phenotype of KCNQ2－related epileptic disorders. These patients have high mortality. Valproate acid is the potentially effective monotherapy for these patients.
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@#Objective To observe the relationship between 7 single nucleotide polymorphisms (SNPs) in KCNQ1 gene region and the effects of exercise intervention on prediatbets. Methods From January, 2015, 70 prediabetes accepted aerobic endurance exercise for twelve weeks. The indexes related to glucose and lipid metabolism were measured before and after intervention. Their genotypes of SNPs were detected with matrix-assisted laser desorption/ionization time of flight mass spectrometry. Results A total of 66 cases finished the tests. Compared with other genotypes of rs2299620, two hours postprandial blood glucose (P2hBG) decreased the most in those with TT genotype (F=5.460, P<0.05). Compared with other haplotypes, P2hBG decreased more in those with C-T haplotype of rs2237897-rs2299620, T-C haplotype of rs2299620-rs151290 and T-T haplotype of rs2299620-rs2237892 (χ2>7.950, P<0.05), fasting insulin decreased more in those with T-C haplotype of rs2237897-rs2299620 (χ2=9.000, P<0.05), and low density lipoprotein decreased more in those with A-C haplotype of rs2283228-rs2237892 (χ2=15.820, P<0.001).Conclusion The prediatbets with TT genotype of rs2299620 and some haplotypes of KCNQ1 are susceptible to exercise intervention in glucose and lipid metabolism.
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Objective To explore the relationship of KCNQ1 rs2237892 polymorphism with type 2 diabetes mellitus(T2DM) in Hefei. Methods A total of 104 healthy individual(control group) and 84 patients with T2DM(T2DM group) were enrolled. The rs2237892 polymorphism KCNQ1 gene was detected by PCR-RFLP. The genetype, allele frequency, related clinical and biochemical data were compared between the two groups. Results There were no significant differences in alleles or genotype frequencies of KCNQ1 rs2237892 gene among control group and T2DM group. The result of Logistic regression analysis showed that the risk of T2DM in the subjects with CT genetype of rs2237892 was 1. 44 times of those with CC genotype(OR =1.44, 95％ CI: 1. 06 ～ 1. 95, P=0. 02). Conclusion KCNQ1 rs2237892 gene may be the susceptibility gene of T2DM in Hefei.
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The pathogenesis of the second major neurodegenerative disorder, Parkinson's disease (PD), is closely associated with the dysfunction of potassium (K) channels. Therefore, PD is also considered to be an ion channel disease or neuronal channelopathy. Mounting evidence has shown that K channels play crucial roles in the regulations of neurotransmitter release, neuronal excitability, and cell volume. Inhibition of K channels enhances the spontaneous firing frequency of nigral dopamine (DA) neurons, induces a transition from tonic firing to burst discharge, and promotes the release of DA in the striatum. Recently, three K channels have been identified to protect DA neurons and to improve the motor and non-motor symptoms in PD animal models: small conductance (SK) channels, A-type K channels, and K7/KCNQ channels. In this review, we summarize the physiological and pharmacological effects of the three K channels. We also describe in detail the laboratory investigations regarding K channels as a potential therapeutic target for PD.
الموضوعات
Animals , Humans , Parkinson Disease , Metabolism , Potassium Channels , Metabolismالملخص
Objective To investigate the gene mutations in benign familial neonatal epilepsy(BFNE) in China.Methods Data of all BFNE probands and their family members were collected from Peking University First Hospital from January 2012 to December 2013.Clinical phenotypes of affected members were analyzed.Genomic DNA was extracted from peripheral blood samples with standard protocol.Mutations in candidate genes mutations were further screened by next-generation sequencing.Results A total of 4 families were collected,from which there were 10 affected members,6 males and 4 females.The age of epilepsy onset was from 1 day to 4 days after birth.The age of last seizure was from 3 days to 3 years and 10 months old.The age of last follow-up was from 4 years and 3 months old to 37 years old.All affected members had normal development.Genetic testing identified KCNQ2 mutations in 3 families (75％,3/4 cases).Two families had missense KCNQ2 mutations (c.1048A ＞ C/p.N350H and c.242T ＞ C/ p.L81P).One family had nonsense KCNQ2 mutation(c.2506G ＞ T/p.E836X).The other 3 KCNQ2 mutations were novel.The remaining BFNE family was not detected with any pathogenic mutation.The age of inital seizure onset of the proband was 1 day after birth.The seizures got controlled at 3 months old.However,this proband had another 2 afebrile seizures during sleep at 3 years and 10 months old.Electroenlephalography monitoring showed focal central temporal spikes.It is speculated that the seizures had evolved into benign epilepsy of childhood with central temporal spikes.Conclusions Mutations in KCNQ2 are major genetic causes in Chinese families with BFNE.KCNQ2 mutation c.1048A ＞ C/p.N350H,c.242T ＞ C/p.L81P,and c.2506G ＞ T/p.E836X are novel mutations.Identification of underlying gene mutation can be helpful for clinical diagnosis and judgment of the prognosis.
الملخص
Abstract Genome-wide association studies have identified several loci associated with an increased risk for cardiovascular disease (CVD) and type 2 diabetes (T2D). Polymorphisms within the KCNQ1 (potassium voltage-gated channel, KQT-like subfamily, member 1) gene are consistently associated with T2D in a number of populations. The current study was undertaken to evaluate the association of 3 polymorphisms of KCNQ1 (rs2237892, rs151290 and rs2237895) with T2D and/or CVD. Patients diagnosed with either T2D (320 patients), CVD (250 patients) or both (60 patients) and 516 healthy controls were genotyped by TaqMan assay run on a real time PCR thermocycler. A statistically significant association was found for SNPs rs151290 (OR = 1.76; 95%CI = 1.02-3.05; p = 0.0435) and rs2237895 (OR = 2.49; 95%CI = 1.72-3.61; p < 0.0001) with CVD. SNP rs151290 (OR = 7.43; 95%CI = 1.00-55.22; p = 0.0499) showed a strong association in patients with both T2D and CVD. None of the SNPs showed any significant association with T2D. Haploview analysis showed that the ACC (rs151290, rs2237892 and rs2237895) haplotype is the most significant risk allele combination for CVD, while CCA is the most significant risk haplotype for co-morbidity with T2D. KCNQ1 polymorphism at SNPs rs151290 and rs2237895 is strongly associated with CVD in this population, but presented no association with T2D.