miR-210-5p promotes epithelial–mesenchymal transition by inhibiting PIK3R5 thereby activating oncogenic autophagy in osteosarcoma cells

• Published in: Cell death & disease 2020-02, Vol.11 (2), p.93-93, Article 93
• Main Authors: Liu, Wei, Jiang, Dongdong, Gong, Fangyi, Huang, Yumin, Luo, Yongjun, Rong, Yuluo, Wang, Jiaxing, Ge, Xuhui, Ji, Chengyue, Fan, Jin, Cai, Weihua
• Format: Article
• Language: English
• Subjects: 13/1; 13/109; 13/51; 14/19; 14/32; 38/77; 631/67/1344; 631/80/39; 82/80; AKT protein; Animals; Antibodies; Autophagy; Biochemistry; Biomedical and Life Sciences; Bone cancer; Bone Neoplasms - enzymology; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Bone tumors; Cell Biology; Cell Culture; Cell Line, Tumor; Cell Movement; Cell Proliferation; Chromosome 5; Epithelial-Mesenchymal Transition; Gene Expression Regulation, Neoplastic; Humans; Immunology; Life Sciences; Mesenchyme; Metastases; Metastasis; Mice, Inbred BALB C; Mice, Nude; MicroRNAs - genetics; MicroRNAs - metabolism; miRNA; Neoplasm Invasiveness; Osteosarcoma; Osteosarcoma - enzymology; Osteosarcoma - genetics; Osteosarcoma - secondary; Osteosarcoma cells; Phagocytosis; Phosphatidylinositol 3-Kinase - genetics; Phosphatidylinositol 3-Kinase - metabolism; Polymerase chain reaction; Proto-Oncogene Proteins c-akt - metabolism; Reverse transcription; Sarcoma; Signal Transduction; TOR protein; TOR Serine-Threonine Kinases - metabolism
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/s41419-020-2270-1

Osteosarcoma (OS) is a malignant bone tumor which occurs mainly in adolescents with frequent pulmonary metastasis and a high mortality rate. Accumulating evidence has indicated that microRNAs (miRNAs) play a vital role in various tumors by modulating target genes as well as signal pathways, and aberrant expression of miRNAs may contribute to OS progression. This study aimed to determine the association between miR-210-5p expression and OS progression and to investigate its potential underlying mechanism. Using reverse transcription-polymerase chain reaction (RT-PCR), miR-210-5p was found to be upregulated in clinical OS specimens and cell lines. Further functional analysis demonstrated that miR-210-5p promoted epithelial–mesenchymal transition (EMT) and induced oncogenic autophagy. Luciferase reporter assay, RNA-ChIP, and western blot analysis confirmed that PIK3R5, an essential regulator in the AKT/mTOR signaling pathway, is a target downstream gene of miR-210-5p. Overexpression or knockdown of PIK3R5 reversed the functional role of overexpression or knockdown of miR-210-5p, respectively. Silencing autophagy-related gene 5 (ATG5) abolished the functional effects of miR-210-5p upregulation or PIK3R5 knockdown in OS cells. In vivo, miR-210-5p overexpression promoted OS tumor growth and pulmonary metastasis. Taken together, our results demonstrated that miR-210-5p promoted EMT and oncogenic autophagy by suppressing the expression of PIK3R5 and regulating the AKT/mTOR signaling pathway. Therefore, inhibition of miR-210-5p may represent a promising treatment for OS.