title: MicroRNA-96 plays an oncogenic role by targeting FOXO1 and regulating AKT/FOXO1/Bim pathway in papillary thyroid carcinoma cells.
abstract: 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.
authors.affiliation: Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
authors.forename: Hong-Ming
authors.initials: HM
authors.lastname: Song
authors.affiliation: Department of General Surgery, Shanghai Tongren Hospital Shanghai 200336, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
authors.forename: Deng-Feng
authors.initials: DF
authors.lastname: Li
authors.affiliation: Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
authors.forename: Chuan-Kui
authors.initials: CK
authors.lastname: Wei
authors.affiliation: Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
authors.forename: Kai-Yao
authors.initials: KY
authors.lastname: Hua
authors.affiliation: Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
authors.forename: Jia-Lu
authors.initials: JL
authors.lastname: Song
authors.affiliation: Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
authors.forename: Niraj
authors.initials: N
authors.lastname: Maskey
authors.affiliation: Department of Breast and Thyroid Surgery, Shanghai Tenth People's Hospital, School of Medicine, Tongji University Shanghai 200072, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Fang
mesh_terms: D017209:Apoptosis / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D015153:Blotting, Western; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism; D002291:Carcinoma, Papillary; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D000077273:Thyroid Cancer, Papillary; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C541492:MIRN96 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt
keywords: FOXO1; K1; TPC1 cells; miR-96; papillary thyroid carcinoma