title: MiR-26a enhances metastasis potential of lung cancer cells via AKT pathway by targeting PTEN.
abstract: 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 β-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 (NFκB) 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.
authors.affiliation: Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenviroment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
authors.forename: Boning
authors.initials: B
authors.lastname: Liu
authors.forename: Xiang
authors.initials: X
authors.lastname: Wu
authors.forename: Bin
authors.initials: B
authors.lastname: Liu
authors.forename: Changli
authors.initials: C
authors.lastname: Wang
authors.forename: Yunde
authors.initials: Y
authors.lastname: Liu
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Zhou
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D000077192:Adenocarcinoma of Lung; D045744:Cell Line, Tumor; D002465:Cell Movement; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology / Q000556:secondary; D008207:Lymphatic Metastasis / Q000473:pathology; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism; D051058:Oncogene Protein v-akt / Q000378:metabolism*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D010766:Phosphorylation; D015533:Transcriptional Activation; D051176:beta Catenin / Q000378:metabolism
chemical_list: D035683:MicroRNAs; D051058:Oncogene Protein v-akt; D051059:PTEN Phosphohydrolase; D051176:beta Catenin; C528163:MIRN26 microRNA, human; C494929:PTEN protein, human