Circ_ANKIB1 stabilizes the regulation of miR-19b on SOCS3/STAT3 pathway to promote osteosarcoma cell growth and invasion
Circ_ANKIB1 stabilizes the regulation of miR-19b on SOCS3/STAT3 pathway to promote osteosarcoma cell growth and invasion
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DOI：
10.1007/s13577-019-00298-6
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发表时间：
2020-01-01
期刊：
影响因子：
4.3
通讯作者：
Li, Xiang
中科院分区：
文献类型：
--
作者：
Du, Yi-xin;Guo, Lin-xin;Li, Xiang
骨肉瘤是一种高度恶性肿瘤。其发生发展的分子机制尚不清楚。目前的研究发现，环状rna （circRNAs）和微rna （miRNAs）等非编码rna在疾病的进展中发挥着重要的调节作用。我们之前的研究表明miR-19b在骨肉瘤中是一个致癌基因。进一步的研究表明circ_ANKIB1具有miR-19b的结合位点，并且这两种分子在骨肉瘤细胞中普遍上调。RIP实验、RNA下拉和双荧光素酶报告基因实验表明circ_ANKIB1可以直接结合miR-19b，在骨肉瘤细胞中作为miR-19b海绵。Circ_ANKIB1促进miR-19b表达，抑制下游靶基因SOCS3的表达，进而激活STAT3通路。当共转染circ_ANKIB1 siRNA和miR-19b模拟物时，SOCS3的表达和STAT3的磷酸化水平没有明显变化。对细胞生长和侵袭的持续检测表明，下调circ_ANKIB1或miR-19b可显著抑制细胞增殖和侵袭，但增加细胞凋亡水平。当circ_ANKIB1 siRNA与miR-19b模拟物或SOCS3 siRNA共转染时，细胞增殖、凋亡和侵袭水平无明显变化，提示circ_ANKIB1可能通过增强miR-19b对下游靶基因SOCS3的调控，影响STAT3通路和骨肉瘤细胞的生长和侵袭。这些发现表明circRNAs稳定了miRNA的功能，进一步研究circRNAs的这一新功能将为肿瘤等疾病的诊断和治疗提供有意义的参考。
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.