miR-573 suppresses pancreatic cancer cell proliferation, migration, and invasion through targeting TSPAN1

miR-573 suppresses pancreatic cancer cell proliferation, migration, and invasion through targeting TSPAN1
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miR-573通过靶向TSPAN1抑制胰腺癌细胞增殖、迁移和侵袭

DOI:
10.1007/s00066-020-01728-3
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发表时间:
2020-12-15
影响因子:
3.1
通讯作者:
Wang, Zhiwei
Wang, Zhiwei
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Lei;Gao, Peng;Wang, Zhiwei

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目的探讨miR-573能否通过靶向TSPAN1抑制胰腺癌细胞的增殖、迁移和侵袭。方法采用RT-qPCR方法检测胰腺癌组织和细胞系中miR-573和TSPAN1的表达。将miR-573Mimic、pcDNA3.1-TSPAN1或genOFFTM st-h-TSPAN1基因导入人胰腺癌细胞系PANC-1。通过CCK-8、集落形成、跨孔迁移和侵袭实验分析miR-573和TSPAN1对细胞增殖、集落形成、迁移和侵袭的影响。利用生物信息学工具筛选miR-573的靶基因,并用双荧光素酶报告基因分析和实时定量聚合酶链式反应进行验证。结果在胰腺癌组织和细胞系中,miR-573表达下调,TSPAN1表达上调。功能分析表明,miR-573过表达抑制了胰腺癌细胞的增殖、克隆形成、迁移和侵袭,并抑制了体内肿瘤的生长。利用生物信息学工具预测miR-573的靶基因,并通过双荧光素酶报告基因分析、RT-qPCR或Western blotting进行验证。TSPAN1的下调也抑制了胰腺癌细胞的细胞增殖、克隆形成、迁移和侵袭。此外,过表达TSPAN1可减弱miR-573对胰腺癌细胞增殖和迁移的抑制作用。结论miR-573通过靶向TSPAN1抑制胰腺癌细胞的增殖、迁移和侵袭。MiR-573靶向的TSPAN1可能成为胰腺癌临床治疗的潜在靶点。
PurposeTo explore whether miR-573 can suppress pancreatic cancer cell proliferation, migration, and invasion by targeting TSPAN1.MethodsThe expression of miR-573 and TSPAN1 in pancreatic cancer tissues and cells lines was analyzed using RT-qPCR. The human pancreatic cancer cell line PANC‑1 was transfected with miR-573 mimic, pcDNA3.1-TSPAN1, or genOFFTM st-h-TSPAN1. The effects of miR-573 and TSPAN1 on cell proliferation, colony formation, migration, and invasion were analyzed by CCK‑8, colony formation, transwell migration, and invasion assay, respectively. Target genes of miR-573 were screened using bioinformatics tools and confirmed by dual-luciferase reporter assay and real-time PCR. The effects of miR-573 in vivo were observed using tumor xenografts.ResultsWe found that miR-573 is downregulated and TSPAN1 is upregulated in pancreatic cancer tissues and cells lines. Function assays demonstrated that overexpression of miR-573 inhibited cell proliferation, colony formation, migration, and invasion of pancreatic cancer cells, as well as suppressing tumor growth in vivo. Target genes of miR-573 were predicted using bioinformatics tools and confirmed by dual-luciferase reporter assay and RT-qPCR or western blotting. Downregulation of TSPAN1 also inhibited cell proliferation, colony formation, migration, and invasion of pancreatic cancer cells. Furthermore, overexpression of TSPAN1 attenuated miR-573-induced inhibition of pancreatic cancer cell proliferation and migration.ConclusionOur findings indicated that miR-573 suppresses pancreatic cancer cell proliferation, migration, and invasion through targeting TSPAN1. TSPAN1 targeted by miR-573 might be a potential therapeutic target for clinical treatment of pancreatic cancer.