Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer
Long noncoding RNA WDFY3-AS2 suppresses tumor progression by acting as a competing endogenous RNA of microRNA-18a in ovarian cancer
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DOI：
10.1002/jcp.29028
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发表时间：
2019-07-25
影响因子：
5.6
通讯作者：
Tan, Wenhua
中科院分区：
文献类型：
--
作者：
Li, Weijia;Ma, Shihong;Tan, Wenhua
卵巢癌（OC）是女性致命的癌症，主要是由于其侵袭性和生存率低。 lncRNA-miRNA-mRNA（长非编码RNA-microRNA-信使RNA）相互作用是改善OC预后的有前途的生物标志物。因此，我们探讨了WDFY3-AS2/miR-18a/RORA轴参与OC细胞生物学活性的调控机制。微阵列分析预测了与OC相关的差异表达的lncRNA、miRNA和mRNA，并研究了它们之间的关系。在 OC 组织和细胞中测量了已鉴定的 lncRNA WDFY3-AS2、miR-18a 和 RORA 的表达模式。进行功能获得和丧失实验来表征 lncRNA WDFY3-AS2 对 OC 细胞的影响，以及 miR-18a 和 RAR 相关孤儿受体 A (RORA) 的参与。体外测定通过体内实验得到验证。根据生物信息学分析，推测WDFY3-AS2通过海绵miR-18a和调节RORA来影响OC。 WDFY3-AS2 和 RORA 在 OC 中表达不足，而 miR-18a 高表达。值得注意的是，WDFY3-AS2 作为竞争性内源 RNA 来海绵 miR-18a 并上调 RORA。过表达WDFY3-AS2或抑制miR-18a后，RORA表达增加，从而抑制OC细胞增殖、迁移、侵袭和上皮间质转化（EMT），并伴有细胞凋亡增强。体内实验证实，过度表达的 WDFY3-AS2 或抑制 miR-18a 可以减少肿瘤生长。综上所述，lncRNA WDFY3-AS2/miR-18a轴通过靶向RORA调节OC的肿瘤进展，为OC的预防和控制提供新的见解。
Ovarian cancer (OC) is a fatal cancer in women, mainly due to its aggressive nature and poor survival rate. The lncRNA-miRNA-mRNA (long noncoding RNA-microRNA-messenger RNA) interaction is promising biomarkers for the improving prognosis of OC. Therefore, we explored the regulatory mechanism of WDFY3-AS2/miR-18a/RORA axis involved in the biological activities of OC cells. Microarray analysis predicted differentially expressed lncRNA, miRNA, and mRNA related to OC, followed by investigating the relationship among them. The expression patterns of the identified lncRNA WDFY3-AS2, miR-18a, and RORA were measured in OC tissue and cells. Gain- and loss-of-function experiments were performed to characterize the effect of lncRNA WDFY3-AS2 on OC cells, as well as the involvement of miR-18a and RAR related orphan receptor A (RORA). The in vitro assays were validated by in vivo experiments. According to bioinformatics analysis, WDFY3-AS2 was speculated to affect OC by sponging miR-18a and modulating RORA. WDFY3-AS2 and RORA were underexpressed in OC, while miR-18a was highly expressed. Notably, WDFY3-AS2 acts as a competing endogenous RNA to sponge miR-18a and upregulate RORA. Upon overexpressing WDFY3-AS2 or inhibiting miR-18a, RORA expression was increased, thereby the OC cell proliferation, migration, invasion, and epithelial-to-mesenchymal transition (EMT) were suppressed, accompanied by enhanced apoptosis. In vivo experiments confirmed that the tumor growth was reduced in response to overexpressed WDFY3-AS2 or inhibited miR-18a. Taken together, the lncRNA WDFY3-AS2/miR-18a axis regulates the tumor progression of OC by targeting RORA, providing new insights for prevention and control of OC.