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微小 RNA100:前列腺癌中一种具有上下文依赖性的 miRNA。

MicroRNA 100: a context dependent miRNA in prostate cancer.

机构信息

Faculdade de Medicina da Universidade de São Paulo, Laboratory of Medical Research, Department of Urology, São Paulo/SP, Brazil.

出版信息

Clinics (Sao Paulo). 2013 Jun;68(6):797-802. doi: 10.6061/clinics/2013(06)12.

Abstract

OBJECTIVE

MicroRNAs are noncoding RNA molecules involved in the development and progression of tumors. We have found that miRNA-100 is underexpressed in metastatic prostate cancer compared to localized disease. Conversely higher levels of miR-100 are related to biochemical recurrence after surgery. This suggests that miR-100 may be a context-dependent miRNA, acting as oncogene or tumor suppressor miRNA. Our aim is to demonstrate the role of miR-100 in the control of predicted target genes in prostate cancer cell lines.

METHODS

Cell lines DU145 and PC3 were transfected with miR-100, antimiR-100 and after 24 h and 48 h of exposure, qRT-PCR and western blot were performed for mTOR, FGFR3, THAP2, SMARCA5 and BAZ2A.

RESULTS

There was reduction in mTOR (p=0.025), THAP2 (p=0.038), SMARCA5 (p=0.001) and BAZ2A (p=0.006) mRNA expression in DU145 cells after exposure to miR-100. In PC3 cells, mTOR expression was decreased by miR-100 (p=0.01). There was a reduction in the expression levels of proteins encoded by studied genes, ranging from 34% to 69%.

CONCLUSIONS

We demonstrate that miR-100 is a context-dependent miRNA controlling BAZ2, mTOR, FGFR3, SMARCA5 and THAP2 that might be involved in PC progression. The elucidation of the roles of miRNAs in tumors is important because they can be used as therapeutic targets in the future.

摘要

目的

微小 RNA 是参与肿瘤发生和发展的非编码 RNA 分子。我们发现,与局限性疾病相比,转移性前列腺癌中 miRNA-100 的表达下调。相反,miR-100 水平较高与手术后生化复发有关。这表明 miR-100 可能是一种上下文依赖的 miRNA,作为癌基因或肿瘤抑制 miRNA 发挥作用。我们的目的是证明 miR-100 在控制前列腺癌细胞系中预测靶基因的作用。

方法

将 miR-100、antimiR-100 转染到 DU145 和 PC3 细胞系中,暴露 24 小时和 48 小时后,进行 qRT-PCR 和 Western blot 检测 mTOR、FGFR3、THAP2、SMARCA5 和 BAZ2A。

结果

DU145 细胞中 miR-100 暴露后,mTOR(p=0.025)、THAP2(p=0.038)、SMARCA5(p=0.001)和 BAZ2A(p=0.006)mRNA 表达降低。PC3 细胞中,mTOR 表达被 miR-100 下调(p=0.01)。研究基因编码的蛋白表达水平降低,范围为 34%至 69%。

结论

我们证明 miR-100 是一种上下文依赖的 miRNA,可调控 BAZ2、mTOR、FGFR3、SMARCA5 和 THAP2,可能参与前列腺癌的进展。阐明 miRNA 在肿瘤中的作用很重要,因为它们将来可以作为治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2b40/3674267/953e398fe249/cln-68-06-797-g001.jpg

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