Long non-coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1.
Long non-coding RNA CASC15 regulates gastric cancer cell proliferation, migration and epithelial mesenchymal transition by targeting CDKN1A and ZEB1.
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长非编码RNA CASC15通过靶向CDKN1A和ZEB1调控胃癌细胞增殖、迁移和上皮间质转化
DOI：
10.1002/1878-0261.12187
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发表时间：
2018-06
影响因子：
6.6
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Wu Q;Xiang S;Ma J;Hui P;Wang T;Meng W;Shi M;Wang Y
长非编码RNA(LncRNA)负责多种细胞功能，如转录和翻译调节以及基因表达的差异。LncRNA CASC15(癌症易感性候选基因15)是位于染色体6p22.3上的一个长长的基因间非编码RNA(LincRNA)基因座。先前的研究表明，lncRNA CASC15与神经母细胞瘤和黑色素瘤等多种癌症的生物学行为有关。在这里，我们旨在详细探讨CASC15如何促进胃癌(GC)的生长。正如预测的那样，QRT-PCR结果显示CASC15在胃癌组织和细胞系中的表达水平高于正常组织和细胞。Kaplan-Meier方法被用来证明CASC15的高表达与GC患者的预后不良有关。此外，功能实验证明，CASC15的下调或上调通过诱导细胞周期停滞和凋亡来抑制或促进细胞的增殖，并通过影响上皮向间充质转化(EMT)的进程来抑制或加速细胞的迁移和侵袭。体内实验表明，CASC15基因的敲除使肿瘤体积和重量减小，并影响EMT过程。Western印迹分析和免疫组织化学证实了这一点，表明裸鼠的转移能力受到了损害。当CASC15与EZH2和WDR5相互作用，调控细胞核内CDKN1A时，CASC15参与胃癌的发生。此外，CASC15基因的敲除引发了ZEB1在细胞质中的沉默，这被证明与CASC15与miR-33a-5p的竞争结合有关。
Long non‐coding RNA (lncRNA) is responsible for a diverse range of cellular functions, such as transcriptional and translational regulation and variance in gene expression. The lncRNA CASC15 (cancer susceptibility candidate 15) is a long intergenic non‐coding RNA (lincRNA) locus in chromosome 6p22.3. Previous research shows that lncRNA CASC15 is implicated in the biological behaviors of several cancers such as neuroblastoma and melanoma. Here, we aimed to explore in detail how CASC15 contributes to the growth of gastric cancer (GC). As predicted, the expression of CASC15 was enriched in GC tissues and cell lines as compared with healthy tissues and cells using qRT‐PCR. The Kaplan–Meier method was used to demonstrate that high expression of CASC15 is linked to a poor prognosis for patients suffering from GC. Additionally, functional experiments proved that the down‐ or up‐regulation of CASC15 inhibited or facilitated cell proliferation via the induction of cell cycle arrest and apoptosis, and also suppressed or accelerated cell migration and invasion by affecting the progression of the epithelial‐to‐mesenchymal transition (EMT). In vivo experiments showed that the knockdown of CASC15 lessened the tumor volume and weight and influenced the EMT process. This was confirmed by western blot assays and immunohistochemistry, indicating impaired metastatic ability in nude mice. CASC15 involvement in the tumorigenesis of GC occurs when CASC15 interacts with EZH2 and WDR5 to modulate CDKN1A in nucleus. Additionally, the knockdown of CASC15 triggered the silencing of ZEB1 in cytoplasm, which was shown to be associated with the competitive binding of CASC15 to miR‐33a‐5p.
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