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circSFMBT1 promotes pancreatic cancer growth and metastasis via targeting miR-330-5p/PAK1 axis.
Cancer Gene Therapy ( IF 6.4 ) Pub Date : 2020-08-28 , DOI: 10.1038/s41417-020-00215-2
Shu Xu 1 , San-Lin Lei 1 , Kui-Jie Liu 1 , Shen-Gen Yi 1 , Zhu-Lin Yang 1 , Hong-Liang Yao 1
Affiliation  

Pancreatic cancer (PC) is one of the most common and lethal cancers that affects millions of people around the world. The prognosis of PC is poor with very limited effective treatments. Here, we fully investigated the function and underlying mechanism of circSFMBT1 (hsa_circ_0066147) in PC. Real-time quantitative PCR, Western blotting, and immunohistochemistry were used to examine levels of circSFMBT1, miR-330-5p, PAK1 (p21-activated kinase 1), or proliferation/metastasis-related proteins. Colony formation assay, flow cytometry, and transwell assay detected the roles of circSFMBT1 and miR-330-5p in cell apoptosis, proliferation, migration, and invasion of PC cells, respectively. Dual luciferase assay and RNA immunoprecipitation were used to validate the interactions of circSFMBT1/miR-330-5p and miR-330-5p/PAK1. Fluorescence in situ hybridization was performed to examine the subcellular localization of circSFMBT1 and miR-330-5p. Subcutaneous tumor growth was monitored in nude mice and in vivo metastasis was examined as well following injection of PC cells into the tail vein. This study demonstrated that circSFMBT1 and PAK1 were up-regulated in PC tissues and cells, while miR-330-5p was down-regulated. circSFMBT1 directly bound miR-330-5p and inhibited its expression. In addition, circSFMBT1 promoted proliferation, migration, and invasion of PC cells through up-regulating proliferation-related proteins and down-regulating apoptosis-related proteins via miR-330-5p. miR-330-5p directly bound PAK1 mRNA and suppressed proliferation, migration, invasion, and epithelial–mesenchymal transition process via targeting PAK1 in PC cells. Further, knockdown circSFMBT1 increased miR-330-5p level, but decreased PAK1 expression and repressed tumor growth and metastasis in vivo. Taken together, circSFMBT1 promotes proliferation and metastasis of PC via regulating miR-330-5p/PAK1 pathway as a miR-330-5p sponge.



中文翻译:

circSFMBT1 通过靶向 miR-330-5p/PAK1 轴促进胰腺癌的生长和转移。

胰腺癌 (PC) 是影响全世界数百万人的最常见和最致命的癌症之一。PC 的预后很差,有效的治疗方法非常有限。在这里,我们充分研究了 circSFMBT1 (hsa_circ_0066147) 在 PC 中的功能和潜在机制。实时定量 PCR、蛋白质印迹和免疫组织化学用于检查 circSFMBT1、miR-330-5p、PAK1(p21 活化激酶 1)或增殖/转移相关蛋白的水平。集落形成试验、流式细胞术和 transwell 试验分别检测了 circSFMBT1 和 miR-330-5p 在 PC 细胞凋亡、增殖、迁移和侵袭中的作用。双荧光素酶测定和 RNA 免疫沉淀用于验证 circSFMBT1/miR-330-5p 和 miR-330-5p/PAK1 的相互作用。进行荧光原位杂交以检查 circSFMBT1 和 miR-330-5p 的亚细胞定位。在裸鼠中监测皮下肿瘤生长,并在将 PC 细胞注射到尾静脉后检查体内转移。该研究表明 circSFMBT1 和 PAK1 在 PC 组织和细胞中上调,而 miR-330-5p 下调。circSFMBT1 直接结合 miR-330-5p 并抑制其表达。此外,circSFMBT1通过miR-330-5p上调增殖相关蛋白和下调凋亡相关蛋白来促进PC细胞的增殖、迁移和侵袭。miR-330-5p 通过靶向 PC 细胞中的 PAK1 直接结合 PAK1 mRNA 并抑制增殖、迁移、侵袭和上皮-间质转化过程。更远,敲低 circSFMBT1 增加 miR-330-5p 水平,但降低 PAK1 表达并抑制体内肿瘤生长和转移。总之,circSFMBT1通过调节miR-330-5p/PAK1通路作为miR-330-5p海绵促进PC的增殖和转移。

更新日期:2020-08-28
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