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The lncRNA SNHG5‐mediated miR‐205‐5p downregulation contributes to the progression of clear cell renal cell carcinoma by targeting ZEB1

机译:lncRNA SNHG5介导的miR-205-5p下调通过靶向ZEB1促进了透明细胞肾细胞癌的进展

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摘要

Recent findings have unraveled the critical functions of the long noncoding RNA (lncRNA) SNHG5 in human malignancies. Nevertheless, the role and mechanism of SNHG5 in clear cell renal cell carcinoma (ccRCC) are still elusive. In our study, substantially higher abundance of SNHG5 was observed in ccRCC specimens and cell lines, and increased SNHG5 expression was intimately correlated with tumor size, tumor‐node‐metastasis (TNM) stage, lymph node invasion, and distant metastases in patients with ccRCC. SNHG5 knockdown obviously suppressed the proliferative, migratory, and invasive capabilities of ccRCC cells, whereas SNHG5 overexpression induced the opposite effects. Mechanistically, SNHG5 activated the transcription of ZEB1, which exerts a pivotal role in modulation of epithelia‐mesenchymal transition (EMT) and tumor metastasis. SNHG5 was then shown to act as an endogenous sponge for miR‐205‐5p, which targets ZEB1 in ccRCC. Moreover rescue experiments revealed that SNHG5 promotes ccRCC cell proliferation, migration, and invasion in a miR‐205‐5p‐dependent manner. Additionally, in vivo assays further indicated that overexpression or silencing of SNHG5 in ccRCC cells promoted or suppressed the tumorigenesis and metastasis, respectively Altogether, the present data provide the first evidence that the lncRNA SNHG5 has an oncogenic role in ccRCC through the SNHG5/miR‐205‐5p/ZEB1 signaling axis and represents a novel potential therapeutic regimen against ccRCC.
机译:最近的发现揭示了长非编码RNA(lncRNA)SNHG5在人类恶性肿瘤中的关键功能。然而,尚不清楚SNHG5在透明细胞肾细胞癌(ccRCC)中的作用和机制。在我们的研究中,ccRCC标本和细胞系中观察到SNHG5的丰度大大提高,并且ccRCC患者中SNHG5表达的增加与肿瘤的大小,肿瘤淋巴结转移(TNM)阶段,淋巴结浸润和远处转移密切相关。 。 SNHG5敲低显然抑制了ccRCC细胞的增殖,迁移和侵袭能力,而SNHG5的过表达诱导相反的作用。从机制上讲,SNHG5激活了ZEB1的转录,这在调节上皮-间质转化(EMT)和肿瘤转移中起着关键作用。然后显示SNHG5充当miR-205-5p的内源海绵,其靶向ccRCC中的ZEB1。此外,救援实验表明SNHG5以miR-205-5p依赖性方式促进ccRCC细胞增殖,迁移和侵袭。此外,体内试验进一步表明,在ccRCC细胞中SNHG5的过表达或沉默分别促进或抑制了肿瘤的发生和转移,目前的数据提供了第一个证据,即lncRNA SNHG5通过SNHG5 / miR-在ccRCC中具有致癌作用。 205-5p / ZEB1信号轴,代表针对ccRCC的新型潜在治疗方案。

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