miR-99a Suppresses the Metastasis of Human Non-Small Cell Lung Cancer Cells by Targeting AKT1 Signaling Pathway

• Published in: Journal of cellular biochemistry Vol. 116; no. 2; pp. 268 - 276
• Main Authors: Yu, Shi-huan, Zhang, Chun-ling, Dong, Fu-shi, Zhang, Yi-mei
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.02.2015; Wiley Subscription Services, Inc
• Subjects: AKT1; Animals; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Line; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Down-Regulation; Female; Gene Expression Regulation, Neoplastic; Humans; Immunoblotting; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Male; MATRIX METALLOPROTEINASE 2; Mice, Inbred BALB C; Mice, Nude; microRNA; MicroRNAs - genetics; Middle Aged; miR-99a; Neoplasm Invasiveness; Neoplasm Metastasis; NON-SMALL CELL LUNG CANCER; Proto-Oncogene Proteins c-akt - genetics; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - genetics; Transplantation, Heterologous; NON-SMALL CELL LUNG CANCER; AKT1; microRNA; miR-99a; MATRIX METALLOPROTEINASE 2
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.24965

ABSTRACT MicroRNAs (miRNAs) play an important role in the development and progression of non‐small cell lung cancer (NSCLC). Recently, several studies have shown that miR‐99a is downregulated in various cancers, which can affect tumor initiation and maintenance. Herein, we found that miR‐99a was downregulated in NSCLC tissues and suppressed tumor metastasis of NSCLC cells. Down‐regulation of miR‐99a is significantly associated with last‐stage and tumor metastasis in NSCLC patients. Further functional experiments found that overexpression of miR‐99a inhibit cell proliferation, migration, and invasion of NSCLC cells in vitro and tumor metastasis of NSCLC in vivo. In addition, we also found that AKT1 is directly involved in miR‐99a‐mediated tumor suppression. Restored the expression of AKT1 partially abolished the suppressive effects miR‐99a on proliferation and invasion of NSCLC cells. Collectively, our data suggest that miR‐99a plays an important role in the tumorigenesis and metastasis of NSCLC and may serve as a therapeutic target to avoid dissemination of NSCLC cells. J. Cell. Biochem. 116: 268–276, 2015. © 2014 Wiley Periodicals, Inc.