Huang Wen-Jie, Wang Yunchao, Liu Songsong, Yang Jiali, Guo Shi-Xiang, Wang Lijiang, Wang Huaizhi, Fan Ying-Fang
Hepatobiliary Surgery, Zhujiang Hospital, Southern Medical University/The Second School of Clinical Medicine, Southern Medical University, Industrial Road No.253, Guangzhou, Guangdong 510280, China; Institute of Hepatopancreatobiliary, Surgery Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan Main Street, Shapingba District, Chongqing 400038, China.
Institute of Hepatopancreatobiliary, Surgery Southwest Hospital, Third Military Medical University (Army Medical University), 30 Gaotanyan Main Street, Shapingba District, Chongqing 400038, China.
Cancer Lett. 2018 May 28;422:70-80. doi: 10.1016/j.canlet.2018.02.014. Epub 2018 Feb 15.
Circular RNAs (CircRNAs) are a novel type of endogenous noncoding RNAs that regulate target gene expression by interacting with microRNA (miRNA). Emerging evidence shows that dysregulation of circRNAs plays important roles in biological and pathological processes, including cancer development and progression. The functional role of circRNA in PDAC (pancreatic ductal adenocarcinoma) remains to be investigated. In this study, high throughput microarray assay revealed that hsa_circ_0000977 was aberrantly up-regulated in pancreatic cancer tissues; this was also validated by qRT-PCR. Silencing hsa_circ_0000977 suppressed pancreatic cancer cell proliferation and induced cell cycle arrest, which was simulated by hsa-miR-874-3p mimics and blocked by hsa-miR-874-3p inhibitor. Bioinformatics analysis predicted that there is an hsa_circ_0000977/hsa-miR-874-3p/PLK1 (Polo like kinase 1) axis in pancreatic cancer progression. Dual-luciferase reporter system and FISH assay validated the direct interaction of hsa_circ_0000977, hsa-miR-874-3p, and PLK1. Western blot verified that inhibition of hsa_circ_0000977 decreased PLK1 expression. Furthermore, silencing hsa_circ_0000977 suppressed pancreatic cancer growth in vivo. Altogether, silencing hsa_circ_0000977 suppresses progression of pancreatic cancer by interacting with hsa-miR-874-3p and decreasing inhibiting PLK1 expression. Our results may provide a promising strategy for future diagnosis and treatment of pancreatic cancer.
环状RNA(CircRNAs)是一类新型的内源性非编码RNA,可通过与微小RNA(miRNA)相互作用来调节靶基因表达。越来越多的证据表明,CircRNAs的失调在包括癌症发生和发展在内的生物学和病理过程中起重要作用。CircRNA在胰腺导管腺癌(PDAC)中的功能作用仍有待研究。在本研究中,高通量微阵列分析显示hsa_circ_0000977在胰腺癌组织中异常上调;qRT-PCR也验证了这一点。沉默hsa_circ_0000977可抑制胰腺癌细胞增殖并诱导细胞周期停滞,hsa-miR-874-3p模拟物可模拟这一作用,而hsa-miR-874-3p抑制剂可阻断这一作用。生物信息学分析预测,在胰腺癌进展过程中存在hsa_circ_0000977/hsa-miR-874-3p/PLK1(Polo样激酶1)轴。双荧光素酶报告系统和FISH分析验证了hsa_circ_0000977、hsa-miR-874-3p和PLK1之间的直接相互作用。蛋白质免疫印迹法证实,抑制hsa_circ_0000977可降低PLK1表达。此外,沉默hsa_circ_0000977可抑制体内胰腺癌的生长。总之,沉默hsa_circ_0000977通过与hsa-miR-874-3p相互作用并降低PLK1表达来抑制胰腺癌的进展。我们的研究结果可能为未来胰腺癌的诊断和治疗提供一种有前景的策略。