Zhang Gang, Liu Song-Lin, Yi Wen-Ting, Dong Yu-Ping, Wan Yin-Xu
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.
Kaohsiung J Med Sci. 2022 Jun;38(6):530-541. doi: 10.1002/kjm2.12527. Epub 2022 Mar 8.
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.
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。