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miRNAs,非小细胞肺癌治疗的潜在靶点。

miRNAs, a potential target in the treatment of Non-Small-Cell Lung Carcinomas.

机构信息

Nantes University, Nantes Atlantique University, IICIMED/ERT-A0902, Cancer du Poumon et Cibles Moléculaires (CPCM), UFR Sciences Pharmaceutiques, Nantes, France.

出版信息

Gene. 2012 Sep 15;506(2):355-9. doi: 10.1016/j.gene.2012.06.008. Epub 2012 Jun 23.

Abstract

Lung cancer is a serious public health problem and Non Small Cell Lung Carcinoma, NSCLC, is particularly resistant to current treatments. So it is important to find new strategies that are active against NSCLC. miRNA is implicated in cancer and may be implicated in NSCLC. Our team has been working on two genes HEF1, a gene implicated in different functions of cell cycle and B2, a large non-coding RNA (nc RNA). These two genes have the same localisation: chromosome 6 and locus p24-25. nc RNA B2 may be involved in the regulation of HEF1. Firstly, we examine a bank of different human miRNAs known to interact with exons of HEF1. HEF1 and B2 were overexpressed in vitro by treating NSCLC-N6 with the cytostatic molecule A190, and carried out qRT-PCR for the expression of miRNA. Secondly, using specific software, we sought for structures originating from the B2 RNA sequence which might interact with HEF1 and assessed their expression. This strategy enabled us to confirm firstly that known miRNAs that can interact with exons of HEF1 are expressed in NSCLC-N6 cells. More precisely this strategy highlighted overexpression of one miRNA, hsa-miR-146b, listed in miRbase. The second step of the studies highlighted the expression of miRNA, potentially sequences originating from B2 in the NSCLC-N6. This miRNA overexpressed might be one of the regulators of the gene HEF1 and consequently implies on the carcinogenesis of lung cancer. So in the future it could be a potential and an innovative way to find a new strategy for the treatment of lung cancer.

摘要

肺癌是一个严重的公共卫生问题,非小细胞肺癌(NSCLC)尤其对当前的治疗方法具有抗性。因此,寻找对 NSCLC 有效的新策略非常重要。miRNA 与癌症有关,可能与 NSCLC 有关。我们的团队一直在研究两个基因 HEF1 和 B2,HEF1 是一个涉及细胞周期不同功能的基因,B2 是一个大型非编码 RNA(ncRNA)。这两个基因具有相同的定位:染色体 6 和 locus p24-25。ncRNA B2 可能参与 HEF1 的调节。首先,我们检查了已知与 HEF1 外显子相互作用的不同人类 miRNA 的数据库。通过用细胞抑制分子 A190 处理 NSCLC-N6,体外过表达 HEF1 和 B2,并进行 miRNA 的 qRT-PCR 表达。其次,我们使用特定的软件,寻找源自 B2 RNA 序列的可能与 HEF1 相互作用的结构,并评估它们的表达。该策略使我们能够首先确认可以与 HEF1 外显子相互作用的已知 miRNA 在 NSCLC-N6 细胞中表达。更确切地说,该策略突出了 miRNA 的过表达,hsa-miR-146b 在 miRbase 中列出。研究的第二步强调了 miRNA 的表达,源自 NSCLC-N6 中的 B2 的潜在序列。这种过表达的 miRNA 可能是 HEF1 基因的一个调节因子,因此暗示了肺癌的癌变。因此,在未来,它可能是寻找治疗肺癌新策略的一种有潜力和创新的方法。

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