CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway.
CircRNA_100782 regulates pancreatic carcinoma proliferation through the IL6-STAT3 pathway.
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DOI：
10.2147/ott.s150678
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发表时间：
2017
影响因子：
4
通讯作者：
Sun J
中科院分区：
文献类型：
--
作者：
Chen G;Shi Y;Zhang Y;Sun J
环状RNA（CircRNA）是一类新型的非编码RNA，在肿瘤中起重要作用。然而，circRNA调节胰腺导管腺癌（PDAC）基因表达的机制仍不清楚。本研究旨在阐明circRNA在PDAC细胞增殖中发挥的作用。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。功能实验显示，circRNA_100782下调抑制BxPC 3细胞增殖和集落形成。功能丧失研究表明，敲低circRNA_100782通过下调microRNA-124（miR-124）靶基因白细胞介素-6受体（IL 6 R）和信号转导和转录激活因子3（STAT 3）抑制细胞增殖。过表达miR-124还通过降低IL 6 R和STAT 3的表达来抑制BxPC 3细胞增殖，这与沉默circRNA_100782的结果一致。此外，荧光素酶测定揭示miR-124是circRNA_100782的直接靶标。沉默STAT 3抑制BxPC 3细胞增殖和集落形成。在用si-circRNA_100782和miR-124模拟物处理的BxPC 3细胞中细胞活力降低，并且这种作用可以通过激活STAT 3来减弱。体内研究验证了circRNA_100782敲低抑制裸鼠中的BxPC 3异种移植物。综上所述，这些结果表明circRNA_100782通过IL 6-STAT 3途径作为miR-124海绵来调节BxPC 3细胞增殖。
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.