MiR-26a enhances metastasis potential of lung cancer cells via AKT pathway by targeting PTEN

BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE

卷:1822

Article

Liu, Boning¹  Wu, Xiang²  Liu, Bin¹  Wang, Changli³  Liu, Yunde⁴  Zhou, Qinghua¹ 

[1] Tianjin Med Univ, Tianjin Key Lab Lung Canc Metastasis & Tumor Micr, Tianjin Lung Canc Inst, Gen Hosp, Tianjin 300052, Peoples R China

[2] Tianjin Med Univ, Core Facil Ctr, Gen Hosp, Tianjin 300052, Peoples R China

[3] Tianjin Med Univ, Tianjin Lung Canc Ctr, Dept Lung Canc Surg, Canc Inst & Hosp, Tianjin 300060, Peoples R China

[4] Tianjin Med Univ, Sch Lab Med, Tianjin 300203, Peoples R China

关键词: MiR-26a;    PTEN;    Lung cancer;    Metastasis;    AKT;   

DOI  :  10.1016/j.bbadis.2012.07.019

来源: Elsevier

【 摘 要 】

Lung cancer is the leading cause of cancer related death, 90% of lung cancer patients die of metastasis. Many microRNAs (miRNAs) are deregulated in cancer. They are involved in tumorigenesis and function as oncogenes or tumor suppressor genes. Recent studies show that miRNAs may be responsible for tumor metastasis. Several functional studies show that miR-26a plays an important role in carcinogenesis; however, none of these studies is related to tumor metastasis. In the present study, we investigated the effect of miR-26a on metastasis potential of lung cancer cells. Our data showed that miR-26a expression level was higher in lymph node metastasis tumor tissues than in primary tumor tissues. Ectopic expression of miR-26a dramatically enhanced lung cancer cell migration and invasion abilities. Metastasis-related genes matrix metallopeptidase 2 (MMP-2), vascular endothelial growth factor (VEGF), Twist and beta-catenin were upregulated. Phosphatase and tensin homolog (PTEN) was a direct target of miR-26a. Further mechanistic study revealed that miR-26a increased AKT phosphorylation and nuclear factor kappa B (NF kappa B) transcriptional activation. Our study demonstrated that miR-26a enhanced lung cancer cell metastasis potential via modulation of metastasis-related gene expression, and activation of AKT pathway by PTEN suppression, suggesting that miR-26a might be a potential therapeutic candidate in patients with metastatic lung cancer. (C) 2012 Elsevier B.V. All rights reserved.

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