首页> 外文期刊>Journal of gastrointestinal surgery: official journal of the Society for Surgery of the Alimentary Tract >Knockdown of microRNA-21 inhibits proliferation and increases cell death by targeting programmed cell death 4 (PDCD4) in pancreatic ductal adenocarcinoma.
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Knockdown of microRNA-21 inhibits proliferation and increases cell death by targeting programmed cell death 4 (PDCD4) in pancreatic ductal adenocarcinoma.

机译:通过靶向胰腺导管腺癌中的程序性细胞死亡4(PDCD4),抑制microRNA-21抑制增殖并增加细胞死亡。

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摘要

OBJECTIVE: This study aims to examine the expression of a panel of five microRNAs (miRNA) in pancreatic ductal adenocarcinoma (PDAC) and the functional effect of miR-21 inhibition in PDAC cell lines. BACKGROUND: miRNA are short, non-coding RNA molecules, which play important roles in several cellular processes by silencing expression of their target genes through translational repression or mRNA degradation. They are often aberrantly expressed in cancer, and this dysregulation can promote carcinogenesis by altering the expression of tumour suppressor or oncogenes. METHODS: miRNA expression levels were measured in 24 PDAC tumour/matched adjacent normal tissue samples and three PDAC cell lines using reverse transcription polymerase chain reaction. Levels of cell proliferation and death and expression of programmed cell death 4 (PDCD4; tumour suppressor) were studied in PDAC cells (MIA-Pa-Ca-2) in the absence or presence of a miR-21 inhibitor. RESULTS: PDAC primary tissues and cell lines displayed a consistent upregulation of miR-21 (P < 0.0001) and downregulation of both miR-148a (P < 0.0001) and miR-375 (P < 0.0001) relative to adjacent normal tissue. Furthermore, miR-21 levels in the primary tumours correlated with disease stage (P < 0.0001). Inhibition of miR-21 in MIA-Pa-Ca-2 PDAC cells led to reduced cell proliferation (P < 0.01) and increased cell death (P < 0.01), with simultaneous increase in levels of the tumour suppressor, PDCD4 (P < 0.01). CONCLUSION: miRNA expression profiles may be used as biomarkers for detecting pancreatic cancer. Moreover, miR-21 could be a predictor of disease progression and a possible therapeutic target in part by upregulating PDCD4 in pancreatic cancer.
机译:目的:本研究旨在检查一组五个微小RNA(miRNA)在胰腺导管腺癌(PDAC)中的表达以及miR-21抑制在PDAC细胞系中的功能作用。背景:miRNA是短的非编码RNA分子,通过翻译抑制或mRNA降解沉默其靶基因的表达,从而在几种细胞过程中发挥重要作用。它们通常在癌症中异常表达,这种失调可通过改变肿瘤抑制因子或癌基因的表达促进癌变。方法:使用逆转录聚合酶链反应检测24个PDAC肿瘤/匹配的邻近正常组织样本和3个PDAC细胞系中的miRNA表达水平。在不存在或存在miR-21抑制剂的情况下,在PDAC细胞(MIA-Pa-Ca-2)中研究了细胞增殖和死亡水平以及程序性细胞死亡4(PDCD4;肿瘤抑制因子)的表达。结果:相对于邻近的正常组织,PDAC主要组织和细胞系显示出miR-21(P <0.0001)的一致上调以及miR-148a(P <0.0001)和miR-375(P <0.0001)的下调。此外,原发性肿瘤中的miR-21水平与疾病阶段相关(P <0.0001)。 miR-21在MIA-Pa-Ca-2 PDAC细胞中的抑制导致细胞增殖减少(P <0.01)和细胞死亡增加(P <0.01),同时肿瘤抑制物PDCD4的水平增加(P <0.01 )。结论:miRNA表达谱可作为检测胰腺癌的生物标志物。而且,miR-21可能是胰腺癌中PDCD4上调的一部分,可能是疾病进展的预测因子和可能的治疗靶标。

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