共查询到20条相似文献,搜索用时 31 毫秒
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Xiao Xie Hong-Tao Liu Ju Mei Fang-Bao Ding Hai-Bo Xiao Feng-Qing Hu Rui Hu Ming-Song Wang 《International journal of clinical and experimental pathology》2015,8(4):3827-3834
MicroRNAs are a class of small non-coding RNAs that play essential roles in cancer development and progression. Recent studies suggested that abnormal expression of miRNAs occurs frequently in non-small cell lung cancer (NSCLC) tissues compared to adjacent normal tissues. In this study, we investigated the expression and the biological roles of miR-106a in non-small cell lung cancer. Our results showed that miR-106a was up-regulated in NSCLC tissues and cell lines. Inhibition of miR-106a in NSCLC cells substantially inhibited cell proliferation, migration, and invasion. Phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-106a, and over-expression of miR-106a suppressed PTEN by direct binding to its 3’-untranslated region (3’-UTR). Furthermore, the presence of miR-106a was inversely correlated with PTEN in NSCLC tissues. Overall, this study suggested that miR-106a inhibited the growth and metastasis of NSCLC cells by decreasing PTEN expression. These data provide novel insights with potential therapeutic applications for the treatment of NSCLC. 相似文献
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Differential microRNA expression tracks neoplastic progression in inflammatory bowel disease-associated colorectal cancer 总被引:1,自引:0,他引:1
Kanaan Z Rai SN Eichenberger MR Barnes C Dworkin AM Weller C Cohen E Roberts H Keskey B Petras RE Crawford NP Galandiuk S 《Human mutation》2012,33(3):551-560
One of the most serious complications faced by patients with inflammatory bowel disease (IBD) is the potential development of colorectal cancer (CRC). There is a compelling need to enhance the accuracy of cancer screening of IBD patients. MicroRNAs (miRNAs) are small nonprotein-coding RNAs that play important roles in CRC oncogenesis. In this study, we report differential miRNA expression in IBD patients with associated CRC from non-neoplastic tissue to dysplasia and eventually cancer. In addition, we identify and examine the role of dysregulated miRNAs in the TP53 pathway. In our CD patients, six miRNAs were upregulated from non-neoplastic tissue to dysplasia, but downregulated from dysplasia to cancer (miR-122, miR-181a, miR-146b-5p, let-7e, miR-17, miR-143) (P < 0.001). Six differentially expressed miRNAs affected the TP53 pathway (miR-122, miR-214, miR-372, miR-15b, let-7e, miR-17) (P < 0.001). Using two human colon cancer cell lines (HT-29 and HCT-116), E2F1, an upstream regulator of TP53, was downregulated in both cell lines transfected with let-7e (P < 0.05) as well as in HCT-116 cells transfected with miR-17 (P < 0.05). Additionally, cyclin G, a cell-cycle regulator miR-122 target was downregulated in both cell lines (P < 0.05). Unique differentially expressed miRNAs were observed in CD-associated CRC progression. Six of these miRNAs had a tumorigenic effect on the TP53 pathway; the effect of three of which was studied using cell lines. 相似文献
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Specific microRNAs modulate embryonic stem cell-derived neurogenesis 总被引:16,自引:0,他引:16
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Chao Ma Tao Huang Yue-Chao Ding Wei Yu Qian Wang Bo Meng Su-Xia Luo 《International journal of clinical and experimental pathology》2015,8(6):6533-6539
Introduction: Cancer stem cells (CSCs) are believed to be ‘seed cell’ in cancer recurrence and metastasis. MicroRNAs (miRNAs) have emerged as potential therapeutic candidates due to their ability to regulate multiple targets involved in tumor progression and chemoresistance. The goal of this study was to investigate the role of miRNA-200c (miR-200c) in regulating colony formation, invasion and chemoresistance of human pancreatic cancer stem cells (PCSCs). Methods: PCSCs with CD24+CD44+ESA+ as the marker was sorted from PANC-1 cell line by fluorescence activated cell sorter (FACS). Quantitative real-time PCR (qRT-PCR) assay was used to detect the expression of miR-200c in PCSCs and PANC-1 cells. Transfection of miR-200c mimic into PCSCs was performed to establish miR-200c over-expressed cells. The effects of overexpressing miR-200c on PCSCs were examined by cell colony forming, invasion and survival assays in vitro. Results: Our data showed that CD24+CD44+ESA+ PCSCs (0.5%) were isolated from PANC-1 cells. Expression of miR-200c was significantly reduced in PCSCs compared with PANC-1 cells. In addition, the capability of colony formation, invasion and chemoresistance were markedly increased in PCSCs than that in PANC-1 cells. Adverse results were obtained in miR-200c overexpressing PCSCs transfected with miR-200c mimic. Conclusion: Our study demonstrated that miR-200c overexpression could decrease colony formation, invasion and chemoresistance of PCSCs. It may become a new therapeutic target for gene therapy in patients suffered from pancreatic cancer. 相似文献
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Bao L Hazari S Mehra S Kaushal D Moroz K Dash S 《The American journal of pathology》2012,180(6):2490-2503
MicroRNAs (miRNAs) are short, noncoding RNA molecules that regulate the expression of a number of genes involved in cancer; therefore, they offer great diagnostic and therapeutic targets. We have developed doxorubicin-resistant and -sensitive metastatic human breast cancer cell lines (MDA-MB-231) to study the chemoresistant mechanisms regulated by miRNAs. We found that doxorubicin localized exclusively to the cytoplasm and was unable to reach the nuclei of resistant tumor cells because of the increased nuclear expression of MDR1/P-glycoprotein (P-gp). An miRNA array between doxorubicin-sensitive and -resistant breast cancer cells showed that reduced expression of miR-298 in doxorubicin-resistant human breast cancer cells was associated with increased expression of P-gp. In a transient transfection experiment, miR-298 directly bound to the MDR1 3' untranslated region and regulated the expression of firefly luciferase reporter in a dose-dependent manner. Overexpression of miR-298 down-regulated P-gp expression, increasing nuclear accumulation of doxorubicin and cytotoxicity in doxorubicin-resistant breast cancer cells. Furthermore, down-regulation of miR-298 increased P-gp expression and induced doxorubicin resistance in sensitive breast cancer cells. In summary, these results suggest that miR-298 directly modulates P-gp expression and is associated with the chemoresistant mechanisms of metastatic human breast cancer. Therefore, miR-298 has diagnostic and therapeutic potential for predicting doxorubicin chemoresistance in human breast cancer. 相似文献
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目的 探讨微小RNA(miRNA)活性分析法筛选前列腺癌去势抵抗转化相关miRNA的效率。方法 应用miRNA活性分析法筛选出在前列腺癌去势抵抗过程中潜在的发挥活性作用的miRNAs。培养人激素敏感型前列腺癌LNCAP细胞(对照组)及人去势抵抗型前列腺癌C4-2细胞(C4-2组)、PC-3细胞(PC-3组)、DU-145细胞(DU-145组),提取各组细胞总RNA,采用实时荧光定量PCR(qPCR)检测miRNAs,比较各组细胞miRNAs的表达情况。结果 应用miRNA活性分析法,依据筛选流程,共选出9个差异表达的miRNAs,分别为miR-1、miR-122、miR-218、miR-145、miR-155、miR-210、miR-197、 miR-346、let-7b。采用qPCR检测这9个miRNAs,结果显示,7个miRNAs在两种不同状态下的前列腺癌细胞中存在差异表达;在不同去势抵抗型前列腺癌细胞中,miR-210、miR-197、miR-346、miR-218均明显高表达,而miR-122、miR-145、let-7b均明显低表达。结论 采用miRNA活性分析法筛选前列腺癌去势抵抗转化相关miRNA,有着较高的准确性与可信度;其具体转化过程还需进一步证实。 相似文献
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Shujun Li Feng Li Ren Niu Helin Zhang Airong Cui Wenting An Xiaolu Wang 《International journal of clinical and experimental pathology》2015,8(7):8048-8056
MicroRNAs (miRNAs) are small, non-coding RNAs of endogenous origin. Accumulating studies have shown aberrant miRNA expression plays an important role in many tumor types. However, the mechanisms by which miRNAs regulate esophageal squamous cell carcinoma (ESCC) development remain poorly understood. In the present study, we assayed expression level of miR-192 in ESCC tissues and cell lines by real-time PCR, and defined the target gene and biological function by luciferase reporter assay, Western blot and apoptosis assay. We first verified that the expression level of miR-192 was significantly increased in ESCC tissues and cancer cells. Moreover, miR-192 over-expression inhibited cells apoptosis and promoted ESCC cells proliferation. We further demonstrated that miR-192 directly targeted 3’-UTR of Bim gene, and inhibited its protein expression. Importantly, Bim could reduce ESCC cells apoptosis ability induced by miR-192. These data suggest an important role of miR-192 in the molecular etiology of ESCC and implicate the potential application of miR-192 in ESCC therapy. 相似文献
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Xiaolei Zhao Zhenhua Zhao Wenchao Xu Junqing Hou Xinyi Du 《International journal of clinical and experimental pathology》2015,8(1):758-764
Introduction: Clear cell renal cell carcinoma (ccRCC) is the most common type of cancer in the adult kidney, and the prognosis of metastatic ccRCC remains poor with high mortality. Recent study indicated that microRNAs (miRNAs) played critical roles in tumor progression. The aim of this study was to investigate the expression, biological role and clinical significance of miR-497 in ccRCC. Methods: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression of miR-497 in renal cancer cell lines and ccRCC tissues. The association between miR-497 expression and overall survival was estimated by the Kaplan-Meier method. Gain of function assays were performed in the 786-O renal cancer cell line. Results: Expression of the miR-497 was significantly decreased in renal cancer cell lines and ccRCC tissues when compared with normal human proximal tubule epithelial cells and adjacent non-tumor tissues. Decreased miR-497 expression was significantly associated with tumor stage, histological grade and lymph node metastases. Significantly shorter overall survival was observed in patients with lower expression of the miR-497. Overexpression of miR-497 significantly inhibited renal cancer cell proliferation, migration and invasion. Conclusions: Our results demonstrated that miR-497 was decreased in ccRCC tissues and may provide a potential prognostic biomarker and a potential target for therapeutic intervention. 相似文献
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背景:研究表明,miRNA对肿瘤干细胞的更新分化有调节作用,有关miRNA-17-92在胃癌干细胞更新及增殖中的作用尚未完全阐明。
目的:分析miRNA-17-92在胃癌干细胞自我更新及增殖中的作用。
方法:①利用细胞培养使胃癌干细胞贴壁分化并送miRNA芯片检测,寻找并验证不断缺失的miRNA。②构建并转染miRNA-17-92分子慢病毒稳定转染细胞。③通过tumorsphere实验研究miRNA-17-92与胃癌细胞更新的关系。④通过MTT、平板克隆试验检测miRNA-17-92与胃癌干细胞增殖的关系。
结果与结论:①miR-19b/20a/92a在胃癌干细胞贴壁分化过程中表达逐渐减低。②慢病毒携带的miRNA-17-19基因在MKN28细胞和CD44-/EpCAM-细胞中的表达均明显增加;瞬时转染pre-miR-19b/20a/92a能使CD44-/EpCAM-和MKN28的miRNA表达增高,瞬时转染pre-miR-19b/20a/92a拮抗剂能使SGC7901和CD44+/EpCAM+的miRNA表达降低;过表达lenti-miR-19b/20a/92a能显著增加胃癌细胞形成肿瘤球的能力;在化疗药的作用下,lenti-miR-19b/20a/92a感染细胞的生存时间延长;瞬时转染pre-miR-19b/20a/92a 能够显著增加CD44+/EpCAM+细胞数,转染其拮抗剂可以降低CD44+/EpCAM+细胞数。③miR-19b/20a/92a稳定表达组的胃癌细胞增殖速度较对照组快。瞬间转染miR-19b/20a/92a前体组加快胃癌细胞的增殖速度,而瞬时转染其拮抗物组减慢胃癌细胞的增殖速度;瞬间转染 miR-19b/20a/92a前体组的克隆数较对照组多,而瞬时转染miR-19b/20a/92a拮抗物组的克隆数较对照组少。结果表明miR-19b/20a/92a基因在胃癌干细胞分化过程中不断缺失,miR-17-92基因能够促进胃癌干细胞的更新和增殖。 中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程 相似文献
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MicroRNAs (miRNAs) are a class of small, non-coding RNA molecules consisting of 19-22 nucleotides that are involved in a variety of biological processes, including development, differentiation, apoptosis and cell proliferation. In cancer research, a growing body of evidence has indicated that miRNAs are aberrantly expressed in many types of human cancers and can function either as tumor suppressors or oncogenes. Bioinformatic predictions suggest that miRNAs regulate more than 30% of protein-coding genes. Aberrant expression of miRNAs in cancer cells causes destruction of miRNA-regulated messenger RNA networks. Therefore, the identification of miRNA-regulated cancer pathways is important for understanding the molecular mechanisms of human cancer. Searching for the aberrant expression of miRNAs in cancer cells is the first step in the functional analysis of miRNAs in cancer cells. Genome-wide miRNA expression signatures can rapidly and precisely reveal aberrant expression of miRNA in cancers. The miRNA expression signatures of human cancers have revealed that miR-375 is significantly downregulated in cancer cells. Our recent data on maxillary sinus, hypopharyngeal and esophageal squamous cell carcinomas have suggested that miR-375 is frequently downregulated and functions as a tumor suppressor that targets several oncogenic genes in cancer cells. In this review, we focus on several types of human squamous cell carcinoma and describe the aberrant expression of miRNAs and the cancer pathways they regulate in these diseases. 相似文献
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Guang-Jian Lu Yu-Qian Dong Qun-Mei Zhang Wen-Yu Di Lu-Yang Jiao Qing-Zu Gao Chen-Guang Zhang 《International journal of clinical and experimental pathology》2015,8(5):5224-5229
Introduction: MicroRNAs (miRNAs) play important roles in tumorigenesis. In this study, we investigated the role of miR-221 in the development and progression of clear cell renal cell carcinoma (ccRCC). Methods: Quantitative real-time PCR (qRT-PCR) was used to measure the expression level of miR-221 in ccRCC tissues and cell lines. Then, we investigated the role of miR-221 to determine its potential roles on renal cancer cell proliferation, migration and invasion in vitro. A luciferase reporter assay was conducted to confirm the target gene of miR-221 and the results were validated in renal cancer cells. Results: In the present study, we found that miR-221 was significantly increased in ccRCC tissues and cell lines. Knocked-down expression of miR-221 remarkably inhibited cell proliferation, migration and invasion of renal cancer cells. Moreover, at the molecular level, our results suggested that TIMP2 as a direct target of miR-221 through which miR-221 promoted tumor cell proliferation, migration and invasion. Conclusions: These findings suggested that miR-221 play an oncogenic role in the renal cancer cell proliferation, migration and invasion by directly inhibiting the tumor suppressor TIMP2, indicating miR-221 act as a potential new therapeutic target for the treatment of ccRCC. 相似文献
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Jingyan Xie ;Mengna Liu ;Yujuan Li ;Yunzhong Nie ;Qiongyu Mi ;Shuli Zhao 《Cellular & molecular immunology》2014,11(5):495-502
MicroRNAs (miRNAs) are a class of small non-coding regulatory RNAs, and changes in miRNAs are involved in tumor origin and progression. Studies have shown that miR-20a is overexpressed in human ovarian cancer tissues and that this miRNA enhances long-term cellular proliferation and invasion capabilities. In this study, a positive correlation between serum miR-20a expression and ovarian cancer stage was observed. We found that miR-20a binds directly to the 3'-untranslated region of MICA/B mRNA, resulting in its degradation and reducing its protein levels on the plasma membrane. Reduction of membrane-bound MICA/B proteins, which are ligands of the natural killer group 2 member D (NKG2D) receptor found on natural killer (NK) cells, y+ T cells and CD8+ T cells, allows tumor cells to evade immune-mediated killing. Notably, antagonizing miR-20a action enhanced the NKG2D-mediated killing of tumor cells in both in vitro and in vivo models of tumors. Taken together, our data indicate that increased levels of miR-20a in tumor cells may indirectly suppress NK cell cytotoxicity by downregulating MICA/B expression. These data provide a potential link between metastasis capability and immune escape of tumor cells from NK cells. 相似文献
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Bissels U Wild S Tomiuk S Hafner M Scheel H Mihailovic A Choi YH Tuschl T Bosio A 《Stem cells (Dayton, Ohio)》2011,29(5):847-857
MicroRNAs (miRNAs) have been shown to play an important role in hematopoiesis. To elucidate the role of miRNAs in the early steps of hematopoiesis, we directly compared donor-matched CD133(+) cells with the more differentiated CD34(+) CD133(-) and CD34(-) CD133(-) cells from bone marrow on the miRNA and mRNA level. Using quantitative whole genome miRNA microarray and sequencing-based profiling, we found that between 109 (CD133(+) ) and 216 (CD34(-) CD133(-) ) miRNAs were expressed. Quantification revealed that the 25 highest expressed miRNAs accounted for 73% of the total miRNA pool. miR-142-3p was the highest expressed miRNA with up to 2,000 copies per cell in CD34(+) CD133(-) cells. Eighteen miRNAs were significantly differentially expressed between CD133(+) and CD34(+) CD133(-) cells. We analyzed their biological role by examining the coexpression of miRNAs and its bioinformatically predicted mRNA targets and luciferase-based reporter assays. We provide the first evidence for a direct regulation of CD133 by miR-142-3p as well as tropomyosin 1 and frizzled homolog 5 by miR-29a. Overexpression of miRNAs in CD133(+) cells demonstrated that miR-142-3p has a negative influence on the overall colony-forming ability. In conclusion, the miRNAs expressed differentially between the CD133(+) and CD34(+) CD133(-) cells are involved in inhibition of differentiation, prevention of apoptosis, and cytoskeletal remodeling. These results are highly relevant for stem cell-based therapies with CD133(+) cells and delineate for the first time how the stem cell character of CD133(+) cells is defined by the expression of specific miRNAs. 相似文献
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Hesheng Li Qinglei Sun Bing Han Xingquan Yu Baoguang Hu Sanyuan Hu 《International journal of clinical and experimental pathology》2015,8(5):4782-4790
Deregulated microRNAs (miRNAs) have been shown to play important roles in cancer progression as a result of changes in expression of their target genes. In this study, we investigated the expression of miR-16b in eight hepatocellular carcinoma (HCC) cell lines, revealed the roles of miR-26b on hepatocellular carcinoma (HCC) cell proliferation, migration, and invasion, and confirmed that EphA2 is a direct target of miR-26b. The miR-26b expression was decreased and EphA2 expression was evaluated in HCC cell lines. Luciferase assays revealed that miR-26b inhibited EphA2 expression by targeting the 3’-untranslated region of EphA2 mRNA. Overexpression of miR-26b dramatically inhibited the proliferation, invasion, and migration of HCC cells by targeting EphA2. Moreover, miR-26b down-regulated c-Myc and CyclinD1 expression, which was reversed by overexpressed EphA2. Taken together, our data demonstrated the mechanism of miR-26b contributed to HCC progression and implicated that miR-26b’s potential in HCC therapy. 相似文献