Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression
Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression
复制标题
DOI：
10.18632/aging.103075
复制
发表时间：
2020-05-15
期刊：
影响因子：
5.2
通讯作者：
Peng, Guanghua
中科院分区：
文献类型：
--
作者：
Dong, Yi;Wan, Guangming;Peng, Guanghua
长基因间隔型非蛋白编码RNA 324(LINC00324)在多种人类肿瘤类型中异常表达，在肿瘤的发生发展中起重要作用。这项研究表明，LINC00324在视网膜母细胞瘤(RB)肿瘤和细胞系中的表达水平高于对照样本。在RB患者中，LINC00324表达增加与TNM分期、视神经侵犯和总生存期缩短密切相关。LINC00324基因敲除可抑制Rb细胞的增殖、克隆形成、迁移和侵袭，在体外促进细胞凋亡和细胞周期停滞，并抑制体内肿瘤生长。在机制方面，LINC00324在RB细胞中与microRNA-769-5p(miR-769-5p)竞争内源RNA。在Rb细胞中，信号转导和转录激活因子3(STAT3)的mRNA被认为是miR-769-5p的直接靶点。补救实验表明，STAT3表达的恢复减弱了miR-769-5p对Rb细胞的抑瘤作用。下调miR-769-5p或恢复STAT3几乎完全逆转LINC00324基因敲除对Rb细胞的影响。我们的发现描述了一个与Rb相关的新的LINC00324-miR-769-5p-STAT3轴，该轴与Rb的体外和体内恶性有关。这项研究可能指向RB的创新治疗靶点。
Long intergenic non-protein-coding RNA 324 (LINC00324) is abnormally expressed in multiple human cancer types and plays an important role in cancer initiation and progression. This study showed that LINC00324 was expressed at higher levels in retinoblastoma (RB) tumors and cell lines than in control samples. Increased LINC00324 expression closely correlated with the TNM stage, optic nerve invasion, and shorter overall survival among patients with RB. The knockdown of LINC00324 decreased RB cell proliferation, colony formation, migration, and invasion, and promoted apoptosis and cell cycle arrest in vitro as well as hindered tumor growth in vivo. With respect to the mechanism, LINC00324 acted as a competing endogenous RNA for microRNA-769-5p (miR-769-5p) in RB cells. The mRNA of signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-769-5p in RB cells. Rescue experiments indicated that restoration of STAT3 expression attenuated the tumor-suppressive actions of miR-769-5p in RB cells. Downregulation of miR-769-5p or restoration of STAT3 almost completely reversed the effects of LINC00324 knockdown on RB cells. Our findings describe a novel RB-related LINC00324-miR-769-5p-STAT3 axis that is implicated in the malignancy of RB in vitro and in vivo. This study may point to innovative therapeutic targets in RB.