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长链非编码RNA ZFPM2-AS1通过miR-130a-3p/ESCO2调控肾细胞癌进展。

Long noncoding RNA ZFPM2-AS1 regulates renal cell carcinoma progression via miR-130a-3p/ESCO2.

作者信息

Zhang Gang, Liu Song-Lin, Yi Wen-Ting, Dong Yu-Ping, Wan Yin-Xu

机构信息

Department of Urology section, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.

Department of Medical Laboratory, Yantai Affiliated Hospital of Binzhou Medical University, Yantai, Shandong, China.

出版信息

Kaohsiung J Med Sci. 2022 Jun;38(6):530-541. doi: 10.1002/kjm2.12527. Epub 2022 Mar 8.

Abstract

Previous studies reported that long noncoding RNA (lncRNA) ZFPM2-AS1 is upregulated in renal cell carcinoma (RCC). However, the biological role of lncRNA ZFPM2-AS1 in RCC has not been explored. In this study, we investigated the role of lncRNA ZFPM2-AS1 in the progression of RCC. Quantitative real-time polymerase chain reaction was used for gene expression analysis, and functional assays including Cell Counting Kit-8 assay, flow cytometry-based apoptosis assay and transwell migration assays were performed to examine the malignant phenotypes. The functional interaction between ZFPM2-AS1 or miR-130A-3P and their targets was detected by dual-luciferase reporter assay. We found that the expressions of ZFPM2-AS1 and ESCO2 were upregulated in RCC tissues and cells, whereas miR-130a-3p was downregulated. The expression level of ZFPM2-AS1 is significantly associated with advanced TNM, distant metastasis, lymphatic metastasis, and a poor overall survival in RCC patients. Silencing ZFPM2-AS1 in RCC cells suppressed cell proliferation, invasion, and migration, and induced cell apoptosis. ZFPM2-AS1 interacted with miR-130A-3P and negatively regulated its expression in RCC cells. We further showed that ESCO2 was a downstream target of miR-130a-3p. Both miR-130a-3p inhibitor and ESCO2 overexpression could rescue the inhibitory effects of ZFPM2-AS1 knockdown in RCC cells. Together, our study demonstrates that ZFPM2-AS1 plays an oncogenic role in RCC progression via the miR-130a-3p/ESCO2 axis.

摘要

先前的研究报道,长链非编码RNA(lncRNA)ZFPM2-AS1在肾细胞癌(RCC)中上调。然而,lncRNA ZFPM2-AS1在RCC中的生物学作用尚未得到探索。在本研究中,我们调查了lncRNA ZFPM2-AS1在RCC进展中的作用。采用定量实时聚合酶链反应进行基因表达分析,并进行包括细胞计数试剂盒-8检测、基于流式细胞术的凋亡检测和Transwell迁移检测等功能实验,以检测恶性表型。通过双荧光素酶报告基因检测检测ZFPM2-AS1或miR-130A-3P与其靶标之间的功能相互作用。我们发现,ZFPM2-AS1和ESCO2在RCC组织和细胞中表达上调,而miR-130a-3p表达下调。ZFPM2-AS1的表达水平与RCC患者的晚期TNM、远处转移、淋巴转移和总体生存率差显著相关。沉默RCC细胞中的ZFPM2-AS1可抑制细胞增殖、侵袭和迁移,并诱导细胞凋亡。ZFPM2-AS1与miR-130A-3P相互作用,并在RCC细胞中负调控其表达。我们进一步表明,ESCO2是miR-130a-3p的下游靶标。miR-130a-3p抑制剂和ESCO2过表达均可挽救ZFPM2-AS1敲低对RCC细胞的抑制作用。总之,我们的研究表明,ZFPM2-AS1通过miR-130a-3p/ESCO2轴在RCC进展中发挥致癌作用。

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