Long noncoding RNA PENG upregulates PDZK1 expression by sponging miR-15b to suppress clear cell renal cell carcinoma cell proliferation
Long noncoding RNA PENG upregulates PDZK1 expression by sponging miR-15b to suppress clear cell renal cell carcinoma cell proliferation
复制标题
长非编码RNA PENG通过海绵miR-15b上调PDZK1表达抑制透明细胞肾细胞癌细胞增殖
DOI：
10.1038/s41388-020-1297-1
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发表时间：
2020-04-27
期刊：
影响因子：
8
通讯作者：
Zheng, Junfang
中科院分区：
文献类型：
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作者：
Qi, Yijun;Ma, Yuanzhen;Zheng, Junfang
据报道，PDZK1 下调可独立预测透明细胞肾细胞癌 (ccRCC) 患者的不良预后，并诱导 ccRCC 的发生和进展。然而，PDZK1 下调的潜在机制仍不清楚。竞争性内源性 RNA (ceRNA) 网络正在成为基因调控的新参与者，并与癌症的发展相关。 ceRNA 通过竞争共享 miRNA 来调节其他 RNA 转录本。为了研究 ceRNA 在 PDZK1 下调和 ccRCC 发展中的作用和机制，我们搜索了调节 ccRCC 组织中 PDZK1 表达的 miRNA 和 lncRNA 的数据库，并评估了它们在 ccRCC 中的作用。我们发现 miR-15b 在 ccRCC 组织中表达水平较高，其上调在临床上与 ccRCC 患者的 PDZK1 水平较低、肿瘤大小较大和生存时间较短有关。相反，一种新的lncRNA（lncPENG）在ccRCC组织中表达水平较低，其下调与miR-15b上调的效应相同。 miR-15b 的下调和 lncPENG 的上调导致 PDZK1 水平显着增加，并在体外和体内抑制增殖。从机制上讲，lncPENG 直接与 miR-15b 结合，并有效地充当 miR-15b 的海绵来调节 PDZK1 的表达。因此，lncPENG可能作为ceRNA来减弱miR-15b依赖性PDZK1下调并抑制细胞增殖，这表明它作为ccRCC的治疗靶点和预后生物标志物可能具有临床价值。
PDZK1 downregulation was reported to independently predict poor prognosis of clear cell renal cell carcinoma (ccRCC) patients and induce ccRCC development and progression. However, the underlying mechanism of PDZK1 downregulation remains unknown. Competing endogenous RNA (ceRNA) networks are emerging as new players in gene regulation and are associated with cancer development. ceRNAs regulate other RNA transcripts by competing for shared miRNAs. To investigate the role and mechanism of ceRNAs in PDZK1 downregulation and the development of ccRCC, we searched databases for miRNAs and lncRNAs that regulate PDZK1 expression in ccRCC tissues and assessed their effects in ccRCC. We found that miR-15b was expressed at higher levels in ccRCC tissues, and its upregulation was clinically associated with lower PDZK1 level, larger tumor size and shorter survival time of ccRCC patients. Conversely, a novel lncRNA (lncPENG) was expressed at a lower level in ccRCC tissues, and its downregulation was associated with the same effects as upregulation of miR-15b. Downregulation of miR-15b and upregulation of lncPENG resulted in a significant increase in PDZK1 level and inhibition of proliferation in vitro and in vivo. Mechanistically, lncPENG directly bound to miR-15b and effectively functioned as a sponge for miR-15b to modulate the expression of PDZK1. Thus, lncPENG may function as a ceRNA to attenuate miR-15b-dependent PDZK1 downregulation and inhibit cell proliferation, suggesting that it may be clinically valuable as a therapeutic target and a prognostic biomarker of ccRCC.