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长链非编码 RNA 肺癌相关转录本 1 通过负调控 miR-495-3p 促进透明细胞肾细胞癌细胞的增殖和侵袭。

Long noncoding RNA lung cancer associated transcript 1 promotes proliferation and invasion of clear cell renal cell carcinoma cells by negatively regulating miR-495-3p.

机构信息

Department of Urology, Tianjin Institute of Urology, The Second Hospital of Tianjin Medical University, Tianjin, China.

Department of Urology, The First Affiliated Hospital of Dalian Medical University, No. 222 Zhongshan Road, Dalian, Liaoning, China.

出版信息

J Cell Biochem. 2018 Sep;119(9):7599-7609. doi: 10.1002/jcb.27099. Epub 2018 Jun 22.

DOI:10.1002/jcb.27099
PMID:29932248
Abstract

Recently, long noncoding RNAs have emerged as new gene regulators and prognostic markers in several cancers, including renal cell carcinoma (RCC). Here, we focused on the long noncoding RNA lung cancer associated transcript 1 (LUCAT1) based on clear cell RCC (ccRCC) the cancer genome atlas (TCGA) data. However, whether aberrant expression of LUCAT1 in ccRCC is correlated with malignancy, metastasis or prognosis has not been elucidated. In the current study, we found that the expression of LUCAT1 was upregulated in ccRCC tissues and cancer cell lines. Upregulated LUCAT1 was positively correlated with larger tumor size, advanced tumor-node-metastasis (TNM) stage, higher smoking frequency, nodal metastasis and shorter overall survival in patients with ccRCC. Inhibition of LUCAT1 by small interfering RNA reduced cell proliferation and invasion of ccRCC cells in vitro. In vivo assay showed that the tumor volume and weight were lower in the group of LUCAT1 inhibition than that in the control group. We then found that LUCAT1 directly bound and inhibited the expression of micoRNA-495-3p (miR-495-3p), which subsequently regulated the expression of special adenine-thymine (AT)-rich DNA-binding protein 1 (SATB1). Collectively, LUCAT1 was critical for proliferation and invasion of ccRCC cells by regulating miR-495-3p and SATB1. Our findings indicated that LUCAT1 and miR-495-3p may offer potential novel therapeutic targets of treatment of ccRCC.

摘要

最近,长链非编码 RNA 已成为几种癌症(包括肾细胞癌[RCC])中新型基因调控因子和预后标志物。在这里,我们根据透明细胞 RCC(ccRCC)癌症基因组图谱(TCGA)数据,重点关注长链非编码 RNA 肺癌相关转录物 1(LUCAT1)。然而,LUCAT1 在 ccRCC 中的异常表达是否与恶性、转移或预后相关尚未阐明。在本研究中,我们发现 LUCAT1 在 ccRCC 组织和癌细胞系中的表达上调。上调的 LUCAT1 与 ccRCC 患者更大的肿瘤大小、更晚期的肿瘤-淋巴结-转移(TNM)分期、更高的吸烟频率、淋巴结转移和更短的总生存期呈正相关。通过小干扰 RNA 抑制 LUCAT1 可降低 ccRCC 细胞的体外增殖和侵袭能力。体内实验表明,与对照组相比,LUCAT1 抑制组的肿瘤体积和重量较低。我们随后发现 LUCAT1 可直接结合并抑制 microRNA-495-3p(miR-495-3p)的表达,进而调节富含特殊腺嘌呤-胸腺嘧啶(AT)的 DNA 结合蛋白 1(SATB1)的表达。总之,LUCAT1 通过调节 miR-495-3p 和 SATB1 对 ccRCC 细胞的增殖和侵袭至关重要。我们的研究结果表明,LUCAT1 和 miR-495-3p 可能为 ccRCC 的治疗提供潜在的新的治疗靶点。

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