Ma Danhui, Chen Sinuo, Wang Heming, Wei Jiayi, Wu Hao, Gao Hong, Cheng Xinlai, Liu Taotao, Luo Shi-Hua, Zhao Yicheng, Song Guangqi
Department of Gastroenterology and Hepatology, Zhongshan Hospital of Fudan University, Shanghai, China.
Shanghai Institute of Liver Diseases, Shanghai, China.
Front Oncol. 2021 Apr 30;11:653061. doi: 10.3389/fonc.2021.653061. eCollection 2021.
Pancreatic cancer is a common malignant tumor with a high incidence and mortality rate. The prognosis of patients with pancreatic cancer is considerably poor due to the lack of effective treatment in clinically. Despite numerous studies have revealed that baicalein, a natural product, is responsible for suppressing multiple cancer cells proliferation, motility and invasion. The mechanism by which baicalein restraining pancreatic cancer progression remains unclear. In this study, we firstly verified that baicalein plays a critical role in inhibiting pancreatic tumorigenesis and . Then we analyzed the alteration of microRNAs (miRNAs) expression levels in Panc-1 cells incubated with DMSO, 50 and 100 μM baicalein by High-Throughput sequencing. Intriguingly, we observed that 20 and 39 miRNAs were accordingly up- and down-regulated through comparing Panc-1 cells exposed to 100 μM baicalein with the control group. Quantitative PCR analysis confirmed that miR-139-3p was the most up-regulated miRNA after baicalein treatment, while miR-196b-5p was the most down-regulated miRNA. Further studies showed that miR-139-3p induced, miR-196b-5p inhibited the apoptosis of Panc-1 cells targeting NOB1 and ING5 respectively. In conclusion, we demonstrated that baicalein is a potent inhibitor against pancreatic cancer by modulating the expression of miR-139-3p or miR-196b-5p.
胰腺癌是一种发病率和死亡率都很高的常见恶性肿瘤。由于临床上缺乏有效的治疗方法,胰腺癌患者的预后相当差。尽管大量研究表明,天然产物黄芩素具有抑制多种癌细胞增殖、运动和侵袭的作用。但黄芩素抑制胰腺癌进展的机制仍不清楚。在本研究中,我们首先证实了黄芩素在抑制胰腺肿瘤发生中起关键作用。然后,我们通过高通量测序分析了用二甲基亚砜(DMSO)、50和100μM黄芩素处理的Panc-1细胞中微小RNA(miRNA)表达水平的变化。有趣的是,通过将暴露于100μM黄芩素的Panc-1细胞与对照组进行比较,我们观察到分别有20个和39个miRNA上调和下调。定量PCR分析证实,黄芩素处理后miR-139-3p是上调最明显的miRNA,而miR-196b-5p是下调最明显的miRNA。进一步研究表明,miR-139-3p通过靶向NOB1、miR-196b-5p通过靶向ING5分别诱导和抑制Panc-1细胞凋亡。总之,我们证明了黄芩素通过调节miR-139-3p或miR-196b-5p的表达是一种有效的胰腺癌抑制剂。