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长链非编码 RNA 小核仁 RNA 宿主基因 12 通过调节 miR-200c-5p/胶原 XI α1 链通路促进肾细胞癌的进展。

lncRNA small nucleolar RNA host gene 12 promotes renal cell carcinoma progression by modulating the miR‑200c‑5p/collagen type XI α1 chain pathway.

机构信息

Department of Urology, Hainan General Hospital, Haikou, Hainan 570105, P.R. China.

Department of Neurology, Hainan General Hospital, Haikou, Hainan 570105, P.R. China.

出版信息

Mol Med Rep. 2020 Nov;22(5):3677-3686. doi: 10.3892/mmr.2020.11490. Epub 2020 Sep 2.

Abstract

Renal cell carcinoma (RCC) is a primary malignant kidney cancer subtype. It has been suggested that long non‑coding RNAs (lncRNAs) serve important roles in the progression of kidney cancer. In fact, the lncRNA small nucleolar RNA host gene 12 (SNHG12) was discovered to be overexpressed in various types of cancer. However, to the best of our knowledge, the role of SNHG12 in RCC remains unclear. The present study aimed to investigate the function of SNHG12 and its underlying molecular mechanism of action in RCC. In patient samples and datasets from The Cancer Genome Atlas. Reverse transcription‑quantitative PCR, demonstrated that SNHG12 expression levels were upregulated in RCC tumor tissues, but not in normal kidney tissues. SNHG12 upregulation was also observed in RCC cell lines. Kaplan‑Meier survival analysis indicated a poor prognosis for those patients with RCC who had upregulated SNHG12 expression levels. Following lentivirus transduction, SNHG12 was successfully knocked down (validated by western blot analysis) and cell migration and invasion assays were performed. SNHG12 knockdown markedly inhibited cell viability and invasion, while increasing apoptosis in both A498 and 786O cell lines. The results of the luciferase reporter assay suggested that SNHG12 exerted its role by sponging microRNA (miR)‑200c‑5p, which led to the upregulation of its target gene, collagen type XI α1 chain (COL11A1). This was further validated, as miR‑200c‑5p inhibition reduced the effects of SNHG12 downregulation on cell viability and apoptosis, without affecting SNHG12 expression levels. Furthermore, the findings indicated that SNHG12 may partially exert its role through COL11A1, which was also upregulated in RCC. In conclusion, the results of the present study suggested that the SNHG12/miR‑200c‑5p/COL11A1 axis may be crucial for RCC progression, which provided an insight into potential therapeutic strategies for RCC treatment.

摘要

肾细胞癌(RCC)是一种主要的恶性肾癌亚型。有研究表明,长链非编码 RNA(lncRNA)在肾癌的进展中发挥着重要作用。事实上,lncRNA 小核仁 RNA 宿主基因 12(SNHG12)已被发现在多种类型的癌症中过度表达。然而,据我们所知,SNHG12 在 RCC 中的作用尚不清楚。本研究旨在探讨 SNHG12 的功能及其在 RCC 中的潜在作用机制。在患者样本和来自癌症基因组图谱的数据集的逆转录-定量 PCR 中,表明 SNHG12 在 RCC 肿瘤组织中的表达水平上调,但在正常肾组织中没有上调。在 RCC 细胞系中也观察到 SNHG12 的上调。Kaplan-Meier 生存分析表明,SNHG12 表达水平上调的 RCC 患者预后较差。通过慢病毒转导,成功敲低了 SNHG12(通过 Western blot 分析验证),并进行了细胞迁移和侵袭试验。SNHG12 敲低显著抑制了 A498 和 786O 细胞系的细胞活力和侵袭,同时增加了细胞凋亡。荧光素酶报告基因检测结果表明,SNHG12 通过海绵 microRNA(miR)-200c-5p 发挥作用,导致其靶基因胶原类型 XI α1 链(COL11A1)的上调。进一步验证表明,miR-200c-5p 抑制减弱了 SNHG12 下调对细胞活力和凋亡的影响,而不影响 SNHG12 的表达水平。此外,研究结果表明,SNHG12 可能部分通过 COL11A1 发挥作用,COL11A1 在 RCC 中也上调。总之,本研究结果表明,SNHG12/miR-200c-5p/COL11A1 轴可能对 RCC 进展至关重要,这为 RCC 治疗提供了潜在的治疗策略。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e0b/7533520/1dcded2fdb96/MMR-22-05-3677-g00.jpg

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