MicroRNA-96 plays an oncogenic role by targeting FOXO1 and regulating AKT/FOXO1/Bim pathway in papillary thyroid carcinoma cells

• Published in: International journal of clinical and experimental pathology 2015-01, Vol.8 (9), p.9889-9900
• Main Authors: Song, Hong-Ming, Luo, Yi, Li, Deng-Feng, Wei, Chuan-Kui, Hua, Kai-Yao, Song, Jia-Lu, Xu, Hui, Maskey, Niraj, Fang, Lin
• Format: Article
• Language: English
• Subjects: Apoptosis - physiology; Apoptosis Regulatory Proteins - metabolism; Bcl-2-Like Protein 11; Blotting, Western; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma, Papillary; Forkhead Box Protein O1; Forkhead Transcription Factors - metabolism; Gene Expression Regulation, Neoplastic - genetics; Humans; Membrane Proteins - metabolism; MicroRNAs - genetics; MicroRNAs - metabolism; Oligonucleotide Array Sequence Analysis; Oncogenes; Original; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction - physiology; Thyroid Cancer, Papillary; Thyroid Neoplasms - genetics; Thyroid Neoplasms - metabolism
• ISSN: 1936-2625

MicroRNAs (miRNAs) are kind of small non-coding RNAs that negatively regulate gene expression at post-transcription level, and those non-coding RNAs appear to play a key role in tumorigenesis. The aim of this study was to investigate the biological role of miR-96 in papillary thyroid carcinoma (PTC) cell lines. We identified miR-96 to be up-regulated in PTC specimens in comparison to matched normal tissues by microRNA microarray and RT-qPCR analysis (P < 0.05). Next, to explore the potential function of miR-96, PTC cell lines K1 and TPC1 were transiently transfected with miR-96 mimics and inhibitor. Successful transfection being confirmed by RT-qPCR. Ectopic expression of miR-96 promoted proliferation and colony formation ability, and inhibited apoptosis of K1 and TPC1 cells, whereas down-regulated expression of miR-96 suppressed those functions when compared with the control cells. According to a computational prediction, FOXO1 maybe a potential target of miR-96. Luciferase assays revealed that miR-96 is directly targeted to both binding sites of FOXO1 3'-untranslated region (3'-UTR) and suppressed the FOXO1 expression, and subsequently inhibited the expression of Bim protein in PTC cells. Moreover, the expression of FOXO1 had an inverse correlation with expression of miR-96 in PTC specimens by RT-qPCR and western blot analysis. The data from the present study demonstrated that miR-96 can promote proliferation, and inhibit apoptosis in PTC cell lines K1 and TPC1, thus miR-96 may play an oncogenic role in PTC by inhibiting the FOXO1 and regulating AKT/FOXO1/Bim pathway, and it may serve as a novel therapeutic target for miRNA-based PTC therapy.