Department of General Surgery, Affiliated Hospital of Nantong University, Nantong University, 226001, Nantong, China.
Department of General Surgery, Nantong Hospital of Traditional Chinese Medicine, Nantong University, 226001, Nantong, China.
Strahlenther Onkol. 2021 May;197(5):438-448. doi: 10.1007/s00066-020-01728-3. Epub 2020 Dec 15.
To explore whether miR-573 can suppress pancreatic cancer cell proliferation, migration, and invasion by targeting TSPAN1.
The 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.
We 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.
Our 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.
通过靶向 TSPAN1 探讨 miR-573 是否可抑制胰腺癌细胞增殖、迁移和侵袭。
采用 RT-qPCR 分析胰腺癌细胞和组织中 miR-573 和 TSPAN1 的表达。用人胰腺癌细胞系 PANC-1 转染 miR-573 模拟物、pcDNA3.1-TSPAN1 或 genOFFTM st-h-TSPAN1。CCK-8 法、集落形成实验、Transwell 迁移和侵袭实验分别分析 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，并通过双荧光素酶报告基因实验和实时 PCR 进行验证。利用肿瘤异种移植观察 miR-573 在体内的作用。
我们发现 miR-573 在胰腺癌细胞和组织中表达下调，而 TSPAN1 表达上调。功能实验表明，过表达 miR-573 可抑制胰腺癌细胞增殖、集落形成、迁移和侵袭，并抑制体内肿瘤生长。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实验和实时 PCR 或 Western blot 进行验证。下调 TSPAN1 也可抑制胰腺癌细胞增殖、集落形成、迁移和侵袭。此外，过表达 TSPAN1 可减弱 miR-573 诱导的胰腺癌细胞增殖和迁移抑制作用。
本研究结果表明，miR-573 通过靶向 TSPAN1 抑制胰腺癌细胞增殖、迁移和侵袭。miR-573 靶向的 TSPAN1 可能是临床治疗胰腺癌的潜在治疗靶点。
