Chen Genwen, Shi Yanting, Zhang Yu, Sun Jianyong
Department of Gastroenterology, Zhongshan Hospital, Fudan University, Shanghai.
Department of Nephrology, Zhongshan Hospital, Fudan University, Shanghai, China.
Onco Targets Ther. 2017 Dec 5;10:5783-5794. doi: 10.2147/OTT.S150678. eCollection 2017.
Circular RNAs (circRNAs) are a novel class of noncoding RNAs that play an important role in cancer. However, the mechanisms by which circRNAs regulate gene expression in pancreatic ductal adenocarcinoma (PDAC) remain unclear. This study seeks to elucidate the role that circRNAs play in the proliferation of PDAC cells. On the basis of previous studies of circRNA expression profiles in PDAC, we found that the circRNA_100782 was markedly upregulated in PDAC tissue. Functional experiments revealed that circRNA_100782 down-regulation inhibited BxPC3 cell proliferation and colony formation. Loss-of-function studies showed that knockdown of circRNA_100782 inhibited cell proliferation by downregulating the microRNA-124 (miR-124) target genes interleukin-6 receptor (IL6R) and signal transducer and activator of transcription 3 (STAT3). Overexpression of miR-124 also inhibited BxPC3 cell proliferation by reducing the expression of IL6R and STAT3, which was consistent with the result of silencing circRNA_100782. In addition, luciferase assay revealed that miR-124 was a direct target of circRNA_100782. Silencing STAT3 inhibited BxPC3 cell proliferation and colony formation. Cell viability was reduced in BxPC3 cells treated with si-circRNA_100782 and miR-124 mimic, and this effect could be attenuated by activating STAT3. In vivo study validated that circRNA_100782 knockdown suppressed BxPC3 xenografts in nude mice. Taken together, these results suggest that circRNA_100782 regulates BxPC3 cell proliferation by acting as miR-124 sponge through the IL6-STAT3 pathway.
环状RNA（circRNAs）是一类新型的非编码RNA，在癌症中发挥重要作用。然而，circRNAs在胰腺导管腺癌（PDAC）中调节基因表达的机制仍不清楚。本研究旨在阐明circRNAs在PDAC细胞增殖中所起的作用。基于先前对PDAC中circRNA表达谱的研究，我们发现circRNA_100782在PDAC组织中显著上调。功能实验表明，circRNA_100782下调可抑制BxPC3细胞增殖和集落形成。功能缺失研究表明，敲低circRNA_100782可通过下调微小RNA-124（miR-124）的靶基因白细胞介素-6受体（IL6R）和信号转导及转录激活因子3（STAT3）来抑制细胞增殖。miR-124的过表达也通过降低IL6R和STAT3的表达来抑制BxPC3细胞增殖，这与沉默circRNA_100782的结果一致。此外，荧光素酶报告基因检测表明miR-124是circRNA_100782的直接靶标。沉默STAT3可抑制BxPC3细胞增殖和集落形成。用si-circRNA_100782和miR-124模拟物处理的BxPC3细胞的细胞活力降低，而激活STAT3可减弱这种作用。体内研究证实，敲低circRNA_100782可抑制裸鼠体内BxPC3异种移植瘤的生长。综上所述，这些结果表明circRNA_100782通过IL6-STAT3途径作为miR-124的海绵来调节BxPC3细胞增殖。
