circRNA hsa_circ_0005909 Predicts Poor Prognosis and Promotes the Growth, Metastasis, and Drug Resistance of Non-Small-Cell Lung Cancer via the miRNA-338-3p/SOX4 Pathway.

circRNA hsa_circ_0005909 Predicts Poor Prognosis and Promotes the Growth, Metastasis, and Drug Resistance of Non-Small-Cell Lung Cancer via the miRNA-338-3p/SOX4 Pathway.
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DOI:
10.1155/2021/8388512
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发表时间:
2021
期刊:
影响因子:
--
通讯作者:
Zhang XY
Zhang XY
中科院分区:
医学4区
文献类型:
--
作者:
Song HM;Meng D;Wang JP;Zhang XY

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环状RNAs(CircRNAs)是调节多种癌症行为的强大因子。已有研究表明,环状RNA hsa_circ_0005909(Circ_0005909)在骨肉瘤中具有调节作用。然而,目前还没有关于CIRC_0005909在非小细胞肺癌进展中是否发挥潜在作用的其他研究。逆转录聚合酶链式反应检测CIRC_0005909在非小细胞肺癌中的表达。采用细胞计数试剂盒8(CCK-8)法、集落形成实验、Transwell实验和裸鼠移植瘤模型实验等方法,研究了C1RC_0005909基因敲除后NSCLC细胞的特异性行为。应用生物信息学和荧光素酶报告基因分析方法研究了CIRC_0005909、miRNA338-3p和Sox4之间的关系。在这项研究中,本课题组首次发现CIRC_0005909在非小细胞肺癌标本和细胞系中的表达明显增加。临床研究表明,CIRC_0005909高表达与非小细胞肺癌患者预后不良有关。在功能上,CIRC_0005909基因的敲除可以抑制非小细胞肺癌细胞的增殖、转移和耐药。在机制上,CIRC_0005909可以作为miRNA-338-3p的海绵,miRNA-338-3p可以靶向Sox4。此外,miRNA338-3p抑制剂还逆转了CIRC_0005909沉默对非小细胞肺癌行为的抑制作用。CIRC_0005909通过调节miRNA338-3p/Sox4轴促进非小细胞肺癌的进展,可能成为非小细胞肺癌的治疗靶点。
Circular RNAs (circRNAs) are powerful factors in regulating various cancer behaviors. It has been manifested in previous researches that circular RNA hsa_circ_0005909 (circ_0005909) exhibits a regulatory function in osteosarcoma. However, there are no other studies on whether circ_0005909 displays potential functions on the progression of non-small-cell lung cancer (NSCLC). RT-PCR was applied to examine the expression of circ_0005909 in NSCLC. To study the specific behaviors of NSCLC cells after circ_0005909 knockdown, cell counting kit-8 (CCK-8) assays, colony formation assays, Transwell assays, and xenograft tumor model assays were conducted. Bioinformatics and luciferase reporter assays were employed to study the association among circ_0005909, miRNA-338-3p, and SOX4. In this research, our group firstly showed that circ_0005909 expressions were distinctly increased in NSCLC specimens and cell lines. Clinical studies revealed that high circ_0005909 expressions were associated with poor prognosis of NSCLC patients. Functionally, knockdown of circ_0005909 was observed to suppress the proliferation, metastasis, and drug resistance of NSCLC cells. In the terms of mechanism, circ_0005909 could act as a sponge of miRNA-338-3p, and miRNA-338-3p could target SOX4. In addition, miRNA-338-3p inhibitors reversed the suppressor ability of circ_0005909 silence on NSCLC behaviors. circ_0005909 promoted the progression of NSCLC via the modulation of the miRNA-338-3p/SOX4 axis, which may be a therapeutic target for NSCLC.
DOI: 10.1038/s41419-021-03533-x
发表时间: 2021-03-05
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