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MiR-140-5p在非小细胞肺癌治疗中的作用

Therapeutic Role of MiR-140-5p for the Treatment of Non-small Cell Lung Cancer.

作者信息

Flamini Valentina, Jiang Wen G, Cui Yuxin

机构信息

Cardiff China Medical Research Collaborative, Cardiff University School of Medicine, Cardiff, U.K.

出版信息

Anticancer Res. 2017 Aug;37(8):4319-4327. doi: 10.21873/anticanres.11825.

Abstract

BACKGROUND/AIM: Lung cancer is the second most common cancer in both men and women, after prostate and breast cancer, respectively. There are two main types of primary lung cancer, non-small cell lung cancer (NSCLC), which accounts for approximately 85-90% of all lung cancer cases, and small cell lung cancer (SCLC), which accounts for the other 10-15% of lung cancers. MiRNAs are small molecules that post-transcriptionally regulate many genes and contribute to many disease aetiologies, including tumours. In lung cancer, the down-regulation of miR-140-5p leads to disease progression.

MATERIALS AND METHODS

In this study a miR-140-5p-only treatment and miR-140-5p combined with other chemotherapeutics have been studied in vitro.

RESULTS

When transfected into NSCLC, the overexpression of miR-140-5p reduced the migration and invasion properties of malignant cells and, also improved their adhesion onto the artificial extracellular matrix. When miRNA-140-5p replacement treatment was combined with other drugs commonly used in clinical practice, such as gefinitib, DMH1 and cisplatin, it enhanced their efficacy by reducing the migration and invasion ability of cancer cells, thus suggesting that it acts synergistically with known compounds for the treatment of NSCLC. Additionally, some endothelial mesenchymal transition (EMT) markers appeared to be regulated by miR-140-5p.

CONCLUSION

Novel direct targets of miR-140-5p have not been investigated in this study, but our results indicate the involvement of miR-140-5p in lung cancer invasion. The preliminary data from this study imply that when miR-140-5p levels are restored; maybe synergistically support current therapies for NSCLC though further validation, especially in vivo is required.

摘要

背景/目的:肺癌是男性和女性中第二常见的癌症,在男性中仅次于前列腺癌,在女性中仅次于乳腺癌。原发性肺癌主要有两种类型,非小细胞肺癌(NSCLC),约占所有肺癌病例的85 - 90%,以及小细胞肺癌(SCLC),占肺癌病例的另外10 - 15%。微小RNA(miRNA)是一类小分子,可在转录后调控许多基因,并与包括肿瘤在内的许多疾病病因有关。在肺癌中,miR - 140 - 5p的下调会导致疾病进展。

材料与方法

在本研究中,对仅使用miR - 140 - 5p治疗以及miR - 140 - 5p与其他化疗药物联合使用进行了体外研究。

结果

当转染到非小细胞肺癌细胞中时,miR - 140 - 5p的过表达降低了恶性细胞的迁移和侵袭特性,并且还改善了它们在人工细胞外基质上的黏附。当miRNA - 140 - 5p替代治疗与临床实践中常用的其他药物(如吉非替尼、DMH1和顺铂)联合使用时,通过降低癌细胞的迁移和侵袭能力增强了它们的疗效,这表明它与已知化合物协同作用以治疗非小细胞肺癌。此外,一些内皮 - 间充质转化(EMT)标志物似乎受miR - 140 - 5p调控。

结论

本研究未对miR - 140 - 5p的新直接靶点进行研究,但我们的结果表明miR - 140 - 5p参与肺癌侵袭。本研究的初步数据表明,当miR - 140 - 5p水平恢复时;可能通过进一步验证协同支持目前的非小细胞肺癌治疗方法,尤其是需要进行体内验证。

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