miR-186-5p Functions as a Tumor Suppressor in Human Osteosarcoma by Targeting FOXK1

• Published in: Cellular physiology and biochemistry Vol. 52; no. 3; pp. 553 - 564
• Main Authors: Zhang, Zhiqiang, Zhang, Wen, Mao, Junsheng, Xu, Zheng, Fan, Mingyu
• Format: Journal Article
• Language: English
• Published: Germany Cell Physiol Biochem Press GmbH & Co KG 2019
• Subjects: 3' Untranslated Regions; Animals; Antagomirs - metabolism; Apoptosis; Bone Neoplasms - metabolism; Bone Neoplasms - mortality; Bone Neoplasms - pathology; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Forkhead Transcription Factors - antagonists & inhibitors; Forkhead Transcription Factors - genetics; Forkhead Transcription Factors - metabolism; Humans; Kaplan-Meier Estimate; Mice; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - antagonists & inhibitors; MicroRNAs - genetics; MicroRNAs - metabolism; Osteosarcoma - metabolism; Osteosarcoma - mortality; Osteosarcoma - pathology; Prognosis; RNA Interference; RNA, Small Interfering - metabolism; Suppressor; FOXK1; miR-186-5p; Osteosarcoma
• ISSN: 1015-8987; 1421-9778; 1421-9778
• DOI: 10.33594/000000039

Aberrantly expressed miRNAs play a vital role in the development of some cancers, such as human osteosarcoma (OS). However, the detailed molecular mechanisms underlying miR-186-5p-involved osteosarcoma are unclear. qRT-PCR and western blot analysis were employed to measure the expressions of miR-186-5p and forkhead box k1 (FOXK1). CCK-8 assay evaluated the effect of miR-186-5p and FOXK1 on cell proliferation. Transwell assay confirmed cell migration and invasion. Eventually, the dual-luciferase reporter assay validated 3'-untranslated region (3'-UTR) of FOXK1 as a direct target of miR-186-5p. Down-regulation of miR-186-5p was identified in OS tissues and cell lines, and negatively correlated with distant metastasis, Enneking stage and poor 5-year prognosis as well as the expression of forkhead box k1 (FOXK1) protein. Further assays demonstrated that miR-186-5p overexpression had inhibitory effects on in-vitro cell proliferation, cell cycle, and in-vivo tumor growth. miR-186-5p overexpression also inhibited the epithelial-tomesenchymal transition (EMT), migration and invasion of OS cells. Importantly, miR-186-5p directly targeted FOXK1 3'-UTR and negatively regulated its expression. Silencing of FOXK1 expression enhanced the inhibitory effects of miR-186-5p on OS cell proliferation, migration and invasion. These findings highlighted miR-186-5p as a tumor suppressor in the regulation of progression and metastatic potential of OS, and may benefit the development of therapies targeting miR-186-5p in patients with OS.