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微小RNA-30e可抑制肺癌细胞生长并增强对吉非替尼的药物敏感性。

MicroRNA-30e reduces cell growth and enhances drug sensitivity to gefitinib in lung carcinoma.

作者信息

Ning Zhi-Qiang, Lu Hai-Lin, Chen Chao, Wang Lin, Cai Wei, Li Yan, Cao Ting-Hua, Zhu Jing, Shu Yong-Qian, Shen Hua

机构信息

Department of Oncology, The First People's Hospital of Wujiang District, Suzhou, 215200, China.

Institute of Medcine, University of Zhengzhou, Henan Province, 450000, China.

出版信息

Oncotarget. 2017 Jan 17;8(3):4572-4581. doi: 10.18632/oncotarget.13944.

Abstract

MicroRNAs (miRNAs) play critical roles in variousbiological processes,including malignancy. Here, we demonstrated that miR-30e levels were markedly reduced in human lung carcinoma specimens in comparisonwith adjacent normal tissues.In addition, miR-30eamounts were starkly lower in the resistant PC9/gefitinib (PC9G) cancer cells compared with PC9 cells. Meanwhile, miR-30eoverexpression inPC9G cells resulted in reduced cell proliferation and migration,reversing drug resistance to gefitinib.Conversely,miR-30e silencing in PC9 cells increased proliferation as well as migration, and conferred resistance to gefitinib.Moreover, HOXA1, which was identified asa new miR-30etarget, plays important roles in regulating cell fate, early developmental patterns and organogenesis.Importantly, miR-30ealso inhibited PC9G growth in vivo. Taken together, these findings demonstrated that miR-30eshould be considered a tumor suppressor miRNA, which could be used in treatinghuman lung cancer.

摘要

微小RNA(miRNA)在包括恶性肿瘤在内的各种生物学过程中发挥着关键作用。在此,我们证明,与相邻正常组织相比,人肺癌标本中miR-30e的水平显著降低。此外,与PC9细胞相比,耐药的PC9/吉非替尼(PC9G)癌细胞中miR-30e的含量明显更低。同时,PC9G细胞中miR-30e的过表达导致细胞增殖和迁移减少,逆转了对吉非替尼的耐药性。相反,PC9细胞中miR-30e的沉默增加了增殖和迁移,并赋予了对吉非替尼的耐药性。此外,HOXA1被确定为一个新的miR-30e靶点,在调节细胞命运、早期发育模式和器官发生中发挥重要作用。重要的是,miR-30e在体内也抑制了PC9G的生长。综上所述,这些发现表明miR-30e应被视为一种肿瘤抑制性miRNA,可用于治疗人类肺癌。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d284/5354855/08be9ad7f6b0/oncotarget-08-4572-g001.jpg

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