Osteosarcoma is a highly malignant tumor. The molecular mechanism of its occurrence and development has not yet been clarified. Current studies have found that noncoding RNAs, such as circular RNAs (circRNAs) and microRNAs (miRNAs), play important regulatory roles in the progression of diseases. Our previous studies have shown that miR-19b is an oncogene in osteosarcoma. Further studies have shown that circ_ANKIB1 has binding sites for miR-19b, and both molecules were generally upregulated in osteosarcoma cells. RIP assay, RNA pull down, and dual-luciferase reporter gene assay showed that circ_ANKIB1 could directly bind to miR-19b and act as an miR-19b sponge in osteosarcoma cells. Circ_ANKIB1 promoted miR-19b expression, inhibited the expression of the downstream target gene SOCS3, and then activated the STAT3 pathway. When cotransfected with circ_ANKIB1 siRNA, and miR-19b mimics, the expression of SOCS3 and the phosphorylation level of STAT3 did not change significantly. Continuous detection of cell growth and invasion showed that the downregulation of circ_ANKIB1 or miR-19b significantly inhibited cell proliferation and invasion, but increased the apoptotic level. When cotransfected with circ_ANKIB1 siRNA and miR-19b mimics or SOCS3 siRNA, the cell proliferation, apoptosis, and invasion levels did not change significantly, suggesting that circ_ANKIB1 could affect the STAT3 pathway and osteosarcoma cell growth and invasion by enhancing the regulation of miR-19b on the downstream target gene SOCS3. These findings suggest that circRNAs stabilize miRNA functions, and further studies on this new function of circRNAs will provide a meaningful reference for the diagnosis and treatment of tumors and other diseases.
Osteosarcoma CircRNA miR-19b SOCS3 STAT3
This is a preview of subscription content, log in to check access.
Compliance with ethical standards
Conflicts of interest
The authors declare that there are no conflicts of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants or animals performed by any of the authors.
Harrison DJ, Geller DS, Gill JD, et al. Current and future therapeutic approaches for osteosarcoma. Expert Rev Anticancer Ther. 2018;18(1):39–50.CrossRefGoogle Scholar
Li X, Yang H, Tian Q, et al. Upregulation of microRNA-17-92 cluster associates with tumor progression and prognosis in osteosarcoma. Neoplasma. 2014;61(4):453–60.CrossRefGoogle Scholar
Li X, Wang FS, Wu ZY, et al. MicroRNA-19b targets Mfn1 to inhibit Mfn1-induced apoptosis in osteosarcoma cells. Neoplasma. 2014;61(3):265–73.CrossRefGoogle Scholar
Fang LL, Wang XH, Sun BF, et al. Expression, regulation and mechanism of action of the miR-17-92 cluster in tumor cells (Review). Int J Mol Med. 2017;40(6):1624–30.PubMedPubMedCentralGoogle Scholar
Jia Z, Wang K, Zhang A, et al. miR-19a and miR-19b overexpression in gliomas. Pathol Oncol Res. 2013;19(4):847–53.CrossRefGoogle Scholar
Jiang T, Ye L, Han Z, et al. miR-19b-3p promotes colon cancer proliferation and oxaliplatin-based chemoresistance by targeting SMAD4: validation by bioinformatics and experimental analyses. J Exp Clin Cancer Res. 2017;36(1):131.CrossRefGoogle Scholar
Fan Y, Yin S, Hao Y, et al. miR-19b promotes tumor growth and metastasis via targeting TP53. RNA. 2014;20(6):765–72.CrossRefGoogle Scholar
Gu Y, Liu S, Zhang X, et al. Oncogenic miR-19a and miR-19b co-regulate tumor suppressor MTUS1 to promote cell proliferation and migration in lung cancer. Protein Cell. 2017;8(6):455–66.CrossRefGoogle Scholar
Rong D, Sun H, Li Z, et al. An emerging function of circRNA-miRNAs-mRNA axis in human diseases. Oncotarget. 2017;8(42):73271–81.CrossRefGoogle Scholar
Meng S, Zhou H, Feng Z, et al. CircRNA: functions and properties of a novel potential biomarker for cancer. Mol Cancer. 2017;16(1):94.CrossRefGoogle Scholar
Xiao-Long M, Kun-Peng Z, Chun-Lin Z. Circular RNA circ_HIPK3 is down-regulated and suppresses cell proliferation, migration and invasion in osteosarcoma. J Cancer. 2018;9(10):1856–62.CrossRefGoogle Scholar
Kun-Peng Z, Xiao-Long M, Lei Z, et al. Screening circular RNA related to chemotherapeutic resistance in osteosarcoma by RNA sequencing. Epigenomics. 2018;10(10):1327–46.CrossRefGoogle Scholar
Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–8.CrossRefGoogle Scholar
Kun-Peng Z, Chun-Lin Z, Jian-Ping H, et al. A novel circulating hsa_circ_0081001 act as a potential biomarker for diagnosis and prognosis of osteosarcoma. Int J Biol Sci. 2018;14(11):1513–20.CrossRefGoogle Scholar
Christopher AF, Gupta M, Bansal P. Micronome revealed miR-19a/b as key regulator of SOCS3 during cancer related inflammation of oral squamous cell carcinoma. Gene. 2016;594(1):30–40.CrossRefGoogle Scholar
Durham GA, Williams JJL, Nasim MT, et al. Targeting SOCS proteins to control JAK-STAT signalling in disease. Trends Pharmacol Sci. 2019;40(5):298–308.CrossRefGoogle Scholar
Namløs HM, Meza-Zepeda LA, Barøy T, et al. Modulation of the osteosarcoma expression phenotype by microRNAs. PLoS One. 2012;7(10):e48086.CrossRefGoogle Scholar
He C, Gao H, Fan X, et al. Identification of a novel miRNA-target gene regulatory network in osteosarcoma by integrating transcriptome analysis. Int J Clin Exp Pathol. 2015;8(7):8348–57.PubMedPubMedCentralGoogle Scholar
Liu G, Huang K, Jie Z, et al. CircFAT1 sponges miR-375 to promote the expression of Yes-associated protein 1 in osteosarcoma cells. Mol Cancer. 2018;17(1):170.CrossRefGoogle Scholar
Piwecka M, Glažar P, Hernandez-Miranda LR, et al. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 2017;357(6357):eaam8526.CrossRefGoogle Scholar
Chen S, Huang V, Xu X, et al. Widespread and functional RNA circularization in localized prostate cancer. Cell. 2019;176(4):831–43.CrossRefGoogle Scholar
Wang Y, Shen Y, Wang S, et al. The role of STAT3 in leading the crosstalk between human cancers and the immune system. Cancer Lett. 2018;415:117–28.CrossRefGoogle Scholar
Li B, Li X. Overexpression of hsa_circ_0007534 predicts unfavorable prognosis for osteosarcoma and regulates cell growth and apoptosis by affecting AKT/GSK-3β signaling pathway. Biomed Pharmacother. 2018;107:860–6.CrossRefGoogle Scholar
Kun-Peng Z, Xiao-Long M, Chun-Lin Z. Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1. Int J Biol Sci. 2018;14(3):321–30.CrossRefGoogle Scholar