lncRNA FLJ26245 regulates the proliferation and migration of prostate cancer PC-3 cells through miR-200a-3p/PTPRG axis / 中国肿瘤生物治疗杂志

@#[摘 要] 目的：探讨lncRNA FLJ26245在前列腺癌组织和细胞中的表达及其对PC-3细胞增殖与迁移能力的影响及其分子机制。方法：选用2017年3月至2019年5月在洛阳中心医院手术切除的52例前列腺癌及相应的癌旁组织标本，以及前列腺细胞系LNCaP、C4-2B、PC-3、DU-145和正常前列腺上皮细胞RWPE-1，用qPCR法检测前列腺癌组织和细胞中FLJ26245的表达水平。分别将FLJ26245 mimic和阴性对照质粒（lncR-NC）转染到PC-3细胞中，用MTT法、细胞划痕愈合实验分别检测细胞的增殖和迁移能力。生物信息学技术预测和双荧光素酶基因报告实验验证FLJ26245与miR-200a-3p、酪氨酸磷酸酶受体G（PTPRG）三者之间的靶向关系。用qPCR和WB法分别检测FLJ26245下游基因及增殖与迁移相关蛋白的表达。结果：FLJ26245在前列腺癌组织和细胞中的表达水平分别显著低于癌旁组织（P<0.01）和RWPE-1细胞（P<0.01或P<0.05），以PC-3细胞中的表达水平为最低（P<0.01）。FLJ26245过表达可明显抑制PC-3细胞的增殖和迁移能力（P<0.05或P<0.01）。FLJ26245可与miR-200a-3p靶向结合，miR-200a-3p可与PTPRG靶向结合（均P<0.01）。FLJ26245过表达的PC-3细胞中miR-200a-3p表达水平显著降低（P<0.01）、PTPRG mRNA和蛋白表达水平均明显升高（均P<0.01），细胞中增殖和迁移相关蛋白cyclin A、CDK2和Twist、N-cadherin均显著降低（均P<0.01）。结论：FLJ26245在前列腺癌组织及细胞中均低表达，其可能通过miR-200a-3p/PTPRG轴调控前列腺癌PC-3细胞的增殖与迁移能力。

Long Noncoding RNA MALAT1 Regulates Hepatocellular Carcinoma Growth Under Hypoxia via Sponging MicroRNA-200a

PURPOSE: Hepatocellular carcinoma (HCC) is a common cancer worldwide. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a long noncoding RNA (lncRNA), has been reported to be aberrantly expressed in hypoxic cancer cells. MALAT1 plays a significant role in many malignancies, including HCC. The aim of this study was to explore the role of MALAT1 in hypoxic HCC cells and its underlying regulatory mechanism. MATERIALS AND METHODS: Quantitative reverse transcription PCR (qRT-PCR) assay was performed to detect the mRNA levels of MALAT1 and microRNA-200a (miR-200a) in HCC cells. Cell invasion and migration ability were evaluated by Transwell assay. Starbase v2.0 and luciferase reporter assay were employed to identify the association between MALAT1 and miR-200a. Cell proliferation and apoptosis were measured by MTT assay and flow cytometry, respectively. RESULTS: MALAT1 levels were significantly upregulated in HCC cells under hypoxia. Hypoxia promoted proliferation, migration, and invasion, and blocked apoptosis in Hep3B cells, which were weakened by knockdown of MALAT1. Starbase v2.0 showed that MALAT1 and miR-200a have a complementarity region, and luciferase reporter assay verified that MALAT1 interacted with miR-200a in Hep3B cells. Moreover, MALAT1 negatively regulated the expression of miR-200a. miR-200a levels were dramatically downregulated in HCC cells under hypoxia. Upregulation of miR-200a inhibited proliferation, migration, and invasion, and induced apoptosis in Hep3B cells under hypoxia. Interestingly, downregulation of miR-200a partially reversed the tumor-suppressive effect of knockdown of MALAT1 on Hep3B cells in hypoxic condition. CONCLUSION: LncRNA MALAT1 was involved in proliferation, migration, invasion, and apoptosis by interacting with miR-200a in hypoxic Hep3B cells, revealing a new mechanism of MALAT1 involved in hypoxic HCC progression.

Detection of expression levels of miR200 family in plasma of breast cancer patients and its significance / 吉林大学学报(医学版)

Objective: To detect the expression levels of microRNA200 (miR200) family in the plasma of the breast cancer patients and the normal controls, and to evaluate their potential values in the screening, progression and prognosis evaluation of breast cancer. Methods: A total of 82 cases of plasma samples of the patients with breast cancer (breast cancer group) and 30 cases of healthy plasma samples (control group) were collected. The microRNAs (miRNAs) were extracted from the plasma samples, the expression levels of miR200 family (miR200a, miR200b, miR200c, miR141 and miR429) were quantified by using real-time PCR technique. The receiver-operating characteristic (ROC) curve was used to assess the diagnostic value of miRNAs, and the associations between the levels of miRNAs and the clinicopathological characteristics were analyzed. Cox proportional hazard mode was used for survival analysis. Results: Compared with control group, the expression level of miR141 in the plasma of the patients in breast cancer group was decreased (P 0 . 05). Concuson: MiR200b and miR141 are likely to become the molecular biological parameters for the diagnosis of breast cancer.

MicroRNA-200a Targets Cannabinoid Receptor 1 and Serotonin Transporter to Increase Visceral Hyperalgesia in Diarrhea-predominant Irritable Bowel Syndrome Rats

BACKGROUND/AIMS: MicroRNAs (miRNAs) were reported to be responsible for intestinal permeability in diarrhea-predominant irritable bowel syndrome (IBS-D) rats in our previous study. However, whether and how miRNAs regulate visceral hypersensitivity in IBS-D remains largely unknown. METHODS: We established the IBS-D rat model and evaluated it using the nociceptive visceral hypersensitivity test, myeloperoxidase activity assay, restraint stress-induced defecation, and electromyographic (EMG) activity. The distal colon was subjected to miRNA microarray analysis followed by isolation and culture of colonic epithelial cells (CECs). Bioinformatic analysis and further experiments, including dual luciferase assays, quantitative real-time polymerase chain reaction, western blot, and enzyme-linked immunosorbent assay, were used to detect the expression of miRNAs and how it regulates visceral hypersensitivity in IBS-D rats. RESULTS: The IBS-D rat model was successfully established. A total of 24 miRNAs were differentially expressed in the distal colon of IBS-D rats; 9 were upregulated and 15 were downregulated. Among them, the most significant upregulation was miR-200a, accompanied by downregulation of cannabinoid receptor 1 (CNR1) and serotonin transporter (SERT). MiR-200a mimic markedly inhibited the expression of CNR1/SERT. Bioinformatic analysis and luciferase assay confirmed that CNR1/SERT are direct targets of miR-200a. Rescue experiments that overexpressed CNR1/SERT significantly abolished the inhibitory effect of miR-200a on the IBS-D rats CECs. CONCLUSIONS: This study suggests that miR-200a could induce visceral hyperalgesia by targeting the downregulation of CNR1 and SERT, aggravating or leading to the development and progression of IBS-D. MiR-200a may be a regulator of visceral hypersensitivity, which provides potential targets for the treatment of IBS-D.

MiR-200a inhibits migration of NSCLC cell line A549 by targeting Sulfatase 2 / 中华胸心血管外科杂志

Objective To investigate the effect of miR-200a on the migratory ability of NSCLC cells and to explore its possible mechanism.Methods Real-time PCR was performed to analyze the miR-200a expression in NSCLC cell lines A549 and SK-MES-1, and human normal lung bronchial epithelial cell line 16HBE.Hsa-miR-200a mimics, NC mimics, hsa-miR-200a inhibitor and NC inhibitor were transfected into A549 cells using Lipofectamine 2000.Migration of A549 cells was detected by Transwell migration assay.The potential target genes of miR-200a were predicted by bioinformatics software and then verified by dual luciferase reporter gene assay and Western blot.Results MiR-200a was significantly down-regulated in A549 and SK-MES-1 cells(P＜0.05).Exogenous over-expression of miR-200a mimics significantly inhibited migratory a-bility of A549 cells, while over-expression of miR-200a inhibitor generated the opposite effect(P＜0.01).Dual luciferase re-porter assay indicated that miR-200a could directly affect the 3'-UTR of Sulf2 gene to inhibit luciferase activity.Western blot revealed that miR-200a expression could significantly reduce Sulf2 protein expression level in A549 cells.Ectopic expression of Sulf2 protein in miR-200a-overexpressing A549 cells overrode the migration inhibition effect of miR-200a, suggesting that targe-ting Sulf2 represents an important mechanism of the anti-tumour activity of miR-200a in lung cancer.Conclusion MiR-200a inhibits migration of lung cancer cells by targeting Sulf2.

Effect of miR-200a on the proliferation, migration and apoptosis of lung cancer cell line A549 / 临床与实验病理学杂志

Purpose To investigate the expression of miR200a in different lung cancer cell lines and its effect on proliferation,migration,and apoptosis in A549 cells.Methods The expressions of miR-200a in different lung cancer cell lines were detected by RT-PCR.miR-200a mimics was transfected into A549 cells by Lipofectamine RNAiMax.The change of proliferation ablility of A549 cells was detected by CCK-8 method and plate clone formation assay.Cell migration was examined by Transwell chamber assay.The flow cytometry was used to examine the changes of apoptosis.The possible target genes of miR-200a were forecasted by bioinformatics tools.Results The results of RT-PCR showed that the expression of miR-200a was significantly down-regulated in A549,H23 and H460 cell lines than 16HBE cell line.CCK-8 assay showed that the OD values of the mimics group at 4,and 5 days were significantly lower than those in the negative control (NC) group (P ＜ 0.05).Plate clone formation assay showed rate of colony formation in the mimics group was significantly lower than that in the NC group [(33.13±0.74)％ vs (45.57 ±1.27)％,P＜0.05].Transwell migration assay showed that the cell number of mimics group that passed the Transwell membrane was significantly lower than that of the NC group [(71.60 ± 17.90) vs (140.20 ± 17.88),P ＜0.05].Flow cytometry showed that the apoptosis rate of the mimics group was significantly higher than that of the NC group [(17.80± 1.90)％ vs (11.33 ± 1.96)％,P ＜ 0.05].Tiam1 may be one of the target gene of miR-200a.Conclusion miR-200a can inhibit the proliferation and migration,and promote apoptosis of lung cancer A549 cells,suggesting a potential new therapeutic agent for lung cancer cell.MiR-200a may play a function of regulation of tumor development through target gene Tiam1.

Effects of miR-200a on the proliferation of lung cancer cells by inhibiting YAP1 / 中国肿瘤临床

Objective: To investigate the effects of miR-200a on the proliferation of lung cancer cells and to identify its direct target genes. Methods:Real-time PCR was performed to analyze the miR-200a expression in 15 paired clinical specimens of non-small cell lung cancer and adjacent noncancerous tissues, human lung cancer cell lines (A549, NCI-H520, and SK-MES-1), and one human normal lung bronchial epithelial cell line (16HBE). The effects of miR-200a on the proliferation of A549 lung cancer cells were detected through CCK-8 method. The candidate target genes of miR-200a were identified by bioinformatics screening and then verified by dual luciferase reporter gene assay, real-time PCR, and Western blot. The effects of YAP1 downregulation on the proliferation of A549 lung cancer cell line were also observed through CCK-8 method. Results:The miR-200a expression in non-small cell lung cancer tissues and lung cancer cell lines was significantly decreased (P<0.01). The upregulation of miR-200a expression could significantly inhibit the pro-liferation of A549 lung cancer cells (P<0.01). Dual luciferase reporter gene indicated that miR-200a could directly affect the 3′-untrans-lated region of the YAP1 gene to inhibit luciferase activity (P<0.01). Real-time PCR and Western blot revealed that the upregulation of miR-200a expression could significantly reduce the mRNA and protein expression levels of YAP1 in A549 lung cancer cells (P<0.01). CCK-8 method indicated that the downregulation of YAP1 could significantly prevent the proliferation of A549 lung cancer cells (P<0.01). Conclusion:MiR-200a inhibits the proliferation of lung cancer cells by targeting YAP1. Thus, miR-200a elicits tumor suppression effects.

MiR-200a and miR-200b target PTEN to regulate the endometrial cancer cell growth in vitro

Objective To study whether miR-200a and miR-200b target PTEN gene expression to regulate the endometrial cancer cell growth in vitro. Methods Endometrial cancer cells ECC-1 were cultured and transfected with the miR-200a and miR-200b mimics and inhibitors as well as the negative control mimics and inhibitors, and then the cell proliferation activity as well as the expression of PTEN and downstream genes in cells was determined; after transfection of miR-200a and miR-200b mimics as well as PTEN-3′UTR luciferase report gene plasmids, the fluorescence activity of luciferase reporter gene was determined. Results 12 h, 24 h and 48 h after transfection, the cell proliferation activity of miR-200a mimics group and miR-200b mimics group were significantly higher than those of NC mimics group while the cell proliferation activity of miR-200a inhibitor group and miR-200b inhibitor group were significantly lower than those of NC inhibitor group; 48 h after transfection, PTEN expression in cells and PTEN-3′UTR luciferase reporter gene fluorescence activity of miR-200a mimics group and miR-200b mimics group were significantly lower than those of NC mimics group while p-PI3K and p-Akt expression were significantly higher than those of NC mimics group; PTEN expression in cells and PTEN-3′UTR luciferase reporter gene fluorescence activity of miR-200a inhibitor group and miR-200b inhibitor group were significantly higher than those of NC inhibitor group while p-PI3K and p-Akt expression were significantly lower than those of NC inhibitor group. Conclusion miR-200a and miR-200b can promote the endometrial cancer cell growth in vitro by targeted inhibition of PTEN gene expression.

MiR-200a and miR-200b target PTEN to regulate the endometrial cancer cell growth in vitro

OBJECTIVE@#To study whether miR-200a and miR-200b target PTEN gene expression to regulate the endometrial cancer cell growth in vitro.@*METHODS@#Endometrial cancer cells ECC-1 were cultured and transfected with the miR-200a and miR-200b mimics and inhibitors as well as the negative control mimics and inhibitors, and then the cell proliferation activity as well as the expression of PTEN and downstream genes in cells was determined; after transfection of miR-200a and miR-200b mimics as well as PTEN-3'UTR luciferase report gene plasmids, the fluorescence activity of luciferase reporter gene was determined.@*RESULTS@#12 h, 24 h and 48 h after transfection, the cell proliferation activity of miR-200a mimics group and miR-200b mimics group were significantly higher than those of NC mimics group while the cell proliferation activity of miR-200a inhibitor group and miR-200b inhibitor group were significantly lower than those of NC inhibitor group; 48 h after transfection, PTEN expression in cells and PTEN-3'UTR luciferase reporter gene fluorescence activity of miR-200a mimics group and miR-200b mimics group were significantly lower than those of NC mimics group while p-PI3K and p-Akt expression were significantly higher than those of NC mimics group; PTEN expression in cells and PTEN-3'UTR luciferase reporter gene fluorescence activity of miR-200a inhibitor group and miR-200b inhibitor group were significantly higher than those of NC inhibitor group while p-PI3K and p-Akt expression were significantly lower than those of NC inhibitor group.@*CONCLUSION@#miR-200a and miR-200b can promote the endometrial cancer cell growth in vitro by targeted inhibition of PTEN gene expression.

miR-200a inhibits cell proliferation by targeting AP-2γexpression in neuroblastoma cells SK-N-AS / 天津医药

Objective To investigate whether miR-200a suppresses cell proliferation by targeting AP-2γexpression, and reveal molecular mechanism that miR-200a functions as a tumor-suppressor in neuroblastoma cells. Methods Dual-luciferase reporter gene assay was employed to examine the effect of miR-200a on AP-2γpromotor luciferase activity. Neu-roblastoma cells were transfected with miR-200a mimics, and the expressions of AP-2γmRNA and protein were detected by RT-PCR and Western blot assay. The effects of AP-2γdown-regulation on cell proliferation were observed after AP-2γshRNA was transfected into neuroblastoma cells. Neuroblastoma cell proliferation was detected by MTS assay after being co-transfected with miR-200a mimics and AP-2γplasmid. Results Results showed that miR-200a could inhibit proliferation of neuroblastoma cells at cell viability (66.33 ± 5.13) compared with that of control group (100 ± 0), and also miR-200a can bind to the 3'untranslated region of AP-2γpromotor and inhibit its luciferase activity with an inhibit ratio at (0.624±0.051). AP-2γmRNA and protein expressions were significantly down-regulated when miR-200a was over-expressed in neuroblas-toma cells. Furthermore, results showed that shRNA-mediated down-regulation of AP-2γthat suppressed the cell prolifera-tion of neuroblastoma at (62.5±2.4) by comparing with the control group (100±0). Moreover, restoring AP-2γexpression re-versed the effect of miR-200a with a cell viability suppression at (92.4±1.4). Conclusion miR-200a suppresses cell prolif-eration by targeting AP-2γexpression in neuroblastoma cells.

MicroRNA-200a is up-regulated in aged rats with erectile dysfunction and could attenuate endothelial function via SIRT1 inhibition / 亚洲男科学杂志(英文版)

MiR-200a was shown to be upregulated in the corpus cavernosum (CC) of rats with aging-related erectile dysfunction (A-ED) in our previous study. Among its target genes, SIRT1 was also reported as a protective factor in erectile function by our groups previously. Thus, miR-200a might attenuate the erectile function in A-ED via SIRT1 inhibition. In the present study, three animal groups were included: aged rats with ED (group AE, n = 8), aged rats with normal erectile function (group AN, n = 8), and young rats as normal controls (group YN, n = 8). CCs from each group were collected for histological and molecular measurements to validate the dysregulation of miR-200a and SIRT1. After that, the cavernous endothelial cells (CECs) from CC of aged rats with normal erectile function were transfected with miR-200a in vitro. Then the expression of SIRT1 and molecules within the eNOS/NO/PKG pathway were measured to investigate whether the transfection could imitate the attenuated process of erectile function in the aged. As a result, miR-200a was upregulated while the SIRT1, the levels of eNOS and cGMP were all downregulated in the CCs from AE group. After transfection in vitro, the miR-200a was upregulated while the SIRT1 and levels of eNOS and cGMP were obviously downregulated. Finally, based on the results of our previous study, we further verify that up-regulation of miR-200a could participate in the mechanisms of A-ED via SIRT1 inhibition, and mainly attenuate endothelial function via influencing the eNOS/NO/PKGpathway.

Expression of miR-200a in peritoneal fibrosis associated with peritoneal dialysis / 中华肾脏病杂志

Objective To find the key miRNA that relative to peritoneal fibrosis associated with peritoneal dialysis (PD) by microarray technology,and verify its expression in vitro and in vivo.Methods The peritoneal fibrosis mouse model associated with PD were established by intraperitoneal injection of lipopolysaccharide (LPS)+ 4.25％ peritoneal dialysate.The expression of miRNA was detected by microarray in peritoneal tissues.The expression of miRNA profiles between fibrotic and normal peritoneal tissues was compared.The differentially expressed miRNA (miR-200a) was validated by real-time PCR in lager sample size cohorts.The expressions of miR-200a were also detected in the epithelial-mesenchymal transition (EMT) process of human peritoneal mesothelium cells.Results In mice model of PD,peritoneal tissue was markedly thickened and with a massive extracellular matrix accumulation.In contrast with control,the expression level of epithelial marker E-cadherin was significantly decreased,α-SMA,Col-Ⅰ and FN were remarkably increased (P ＜ 0.05).By miRNA microarray analysis,miR-200a was significantly down-regulated (3.31 folds change,P ＜ 0.05) in fibrotic peritoneal tissues.The down-regulated expression level of miR-200a was also validated by realtime PCR in larger cohorts (P ＜ 0.05).Then,the expression level of miR-200a was detected in the EMT process of human peritoneal mesothelium cells.During the process of TGF-β1 induced EMT,miR -200a was significantly down-regulated compared with the control (P ＜ 0.05).Conclusions Downregulated expression of miR-200a was observed both during peritoneal fibrosis and TGF-β 1 induced EMT in vivo and in vitro,suggesting that miR-200a may be involved in the peritoneum fibrosis by regulating the target genes of EMT.

Up-regulation of miR-200 a attenuates TGF-β1-induced activation and collagen synthesis in rat pancreatic stellate cells / 基础医学与临床

Objective To investigate the effect of miR-200 a mimic on transforming growth factor β1-mediated acti-vation and collagen secretion of rat pancreatic stellate cells .Methods PSCs were isolated and cultured from pan-creatic tissue and identified by desmin , GFAP and α-SMA immunofluorescence staining .PSCs of 2nd generation were divided into control group , TGF-β1 group, TGF-β1+miR-NC group and TGF-β1+miR-200a mimic group.α-SMA and collagen Ⅰ protein were measured by Western blot and immunofluorescence staining .The mRNA ofα-SMA and collagen Ⅰ and the expression of miR-200a were detected by quantitative real-time PCR.Results TGF-β1 stimulates the activation of PSCs and promote collagen synthesis in time-dependment manner ( P<0.05 ) . After transfection of the mimic , treating with the same concentration of TGF-β1, the expressions of protein and mR-NA of both α-SMA and collagen Ⅰ decreases significantly ( P<0.01 ) .Conclusions Over-expression of miR-200 a significantly attenuates α-SMA activity and further affects the collagen synthesis of TGF-β1-dependent activa-tion of PSCs.The mechanisms are potentially related to the biological effects of TGF-β1.

Expression and clinical significance of four miRNAs in epithelial ovarian cancer / 天津医药

Objective To determine the expressions of miR-200a, miR-141, miR-205 and miR-34a in epithelial ovarian cancer (EOC) samples and to explore their clinical significance. Methods According to FIGO staging, 44 EOC pa?tients were divided into two groups:early FIGO stage (stageⅠ-Ⅱ, n=15) and late FIGO stage (stageⅢ-Ⅳ, n=29). Expres?sions of 4 miRNAs were detected by real time quantitative PCR, and were compared between two groups. The correlation of 4 miRNAs was calculated. EOC patients were divided into high miRNA expression group and low expression group according to the median value of miRNAs expression. Kaplan-Meier survival analysis and Cox multivariate analysis were used to com?pare the age, FIGO state, tumor residual after operation and post-operative chemotherapy of ovarian cancer between two groups. Results The expression of miR-141 was elevated in stagesⅢandⅣcompared with that of stagesⅠand Ⅱ(P=0.036). There was a positive correlation between expression of miR-141, miR-200a and miR-205, but a negative correlation with miR-34a (P<0.05). There was a positive correlation between miR-200a and miR-205 (P<0.05). Lower miR-200a ex?pression was associated with shorter progress free survival in ovarian cancer analyzed by log-rank test ( P=0.035). The sur?vival rate was significantly higher in FIGO stages ⅠandⅡthan that of FIGO stagesⅢandⅣ(P<0.05). Cox regression analysis revealed that miR-200a, FIGO stage and age were influential factors of overall survival time and progress-free sur?vival time of ovarian cancer, while miR-141, miR-205, miR-34a and tumor residual after operation and post-operative che?motherapy were not influential factors. Conclusion The expression of miR-200a is closely correlated with the progress and prognosis of ovarian cancer and may be used as an independent indicator for ovarian cancer prognosis.

Expression of miR-200 a and PTEN in colorectal carcinoma and their clinical significance / 临床与实验病理学杂志

Purpose To investigate the expression of miR-200a and PTEN in colorectal carcinoma (CRC) and their relationships with clinicopathologic features. Methods In situ hybridization and immunohistochemistry ( EnVision method) for miR-200a and PTEN were performed in 87 CRCs and normal colorectal tissues distant from tumors. Relationship between expression of miR-200a and PTEN and clinicopathologic parameters of CRC was also analyzed. Results The in situ hybridization showed that the positive expression rate of the miR-200a in CRC was higher than those in normal colorectal mucosa (P0. 05). The expression of miR-200a had a close negative correlation to that of PTEN in CRC (P<0. 01). Conclusions Overexpression of miR-200a might be associated with the occurrence and development by targeting PTEN, and they could be the indicators in the early diagnosis,treatment and prognosis of CRC.

Expression and clinical significance of miR-200a in childhood B-cell acute lymphoblastic leukemia / 临床儿科杂志

Objective To explore the expression and clinical signiifcance of microRNA-200a in childhood B-cell acute lymphoblastic leukemia (ALL). Methods Bone marrow samples were collected from 45 children with B-cell ALL and 18 chil-dren without hematology disease as control. Total RNA was acquired from bone marrow. qRT-PCR was performed to detect the expression level of miR-200a. Results The relative expression level of miR-200a in B-cell ALL group was signiifcantly lower than that in control group (P<0.05);the expression of miR-200a in children over 10 years old was signiifcantly lower than those in children under 10 years old (P<0.05);the expression of miR-200a in newly diagnosed samples was lower than those in those samples taken on Day 33 and at Week 12, respectively (P<0.05, P<0.01). In addition, the expression of miR-200a in low-risk group was higher than those in mid-risk and high-risk group, respectively (P<0.05). Conclusions Low level of miR-200a had a close correlation with the development and prognosis of childhood B cell ALL, which could be used as a potential target of thera-py and a biomarker of childhood B cell ALL in the future.

MiR-200a enhances the migrations of A549 and SK-MES-1 cells by regulating the expression of TSPAN1.

MicroRNA-200a (miR-200a) has been reported to regulate tumour progression in several tumours; however, little is known about its role in non-small cell lung cancer cells (NSCLCs). Here, we found that miR-200a was up-regulated in A549 and SK-MES-1 cells compared with normal lung cells HELF. By a series of gain-of-function and loss-offunction studies, over-expression of miR-200a was indicated to enhance cells migration, and its knock-down inhibited migration of cells in NSCLC cell lines. Furthermore, miR-200a was identified to induce TSPAN1 expression which was related to migration. TSPAN1 was proved to induce migration, and so up-regulation of TSPAN1 by miR-200a may explain why over-expressing miR-200a promotes NSCLC cells migration.

Identification of Genes Regulated by IL-1beta Using Integrative microRNA and mRNA Genomic Analysis in Human Articular Chondrocytes

OBJECTIVE: The physiological and pathogenetic role of microRNAs (miRNAs) in the maintenance of joint homeostasis and in the development of arthritis is recently being elucidated. In this study, we attempted to identify differentially expressed miRNAs in human osteoarthritis (OA) chondrocytes in response to interleukin (IL)-1beta. In addition, simultaneous profiling of miRNA and mRNA expression was performed to get an integrated analysis of miRNA and mRNA expression. METHODS: Monolayer cultured chondrocytes obtained from knee cartilages of OA patients were stimulated with IL-1beta for 4 hours and RNA was isolated. One microgram of total RNA was polyadenylated and converted to cDNA and miRNA microarray was performed. Seven hundred thirty five oligos were used, corresponding to 470 well-annotated human miRNA sequences and 265 potential miRNAs that were identified recently. mRNA microarray was performed simultaneously using the RNA samples that were used for miRNA array. Both sequence and expression information was used to identify regulatory relationship between miRNA and mRNA pairs. RESULTS: Expression profiling of miRNA extracted from IL-1beta treated chondrocytes identified 25 miRNA which showed differential expression. We also identified 7190 mRNAs differentially regulated by IL-1beta treatment. Among the 25 miRNAs differentially regulated, 13 miRNAs had targets searched by MiRANDA scheme. By combining target search and miRNA-mRNA pairing, we could identify 1043 miRNA-mRNA target pairs. MiR-200a was found to be expressed in human OA and normal cartilages, with downregulation in OA lesion cartilages. CONCLUSION: It is suggested that miRNA may play a role in the regulation of cartilage degradation in OA.