Pancreatic ductal adenocarcinoma (PDAC) is a lethal human malignancy, and previous researches support the contribution of microRNA (miRNA) to cancer progression. MiR-122-5p is reported to participate in the regulation of various cancers, while the function of miR-122-5p in PDAC remains unclear. In this study, we investigated the precise mechanism of miR-122-5p involved in PDAC pathogenesis. The expression levels of miR-122-5p were detected in human PDAC tissues and cell lines by miRNA RT-PCR. The effects of miR-122-5p on cell proliferation were explored by MTT assays, colony formation assays and flow cytometry assays. The ability of migration and invasion was determined by transwell assays. Dual Luciferase reporter assay was performed to validate the direct interaction between miR-122-5p and its target gene. The related molecules of cell cycle, apoptosis and epithelial–mesenchymal transition (EMT) were examined with qRT-PCR and western blot. In addition, xenograft mouse models were applied to explore the effects of miR-122-5p in vivo. MiR-122-5p was underexpressed, while CCNG1 was highly expressed in PDAC tissues and cells. MiR-122-5p was negatively correlated with TNM stage, tumor size and lymph node metastasis in PDAC patients. Overexpression of miR-122-5p suppressed the proliferation, migration and invasion in vitro and inhibited tumorigenesis in vivo. Furthermore, CCNG1 was a direct target of miR-122-5p. Upregulated CCNG1 could partially reverse the effects caused by miR-122-5p. Moreover, miR-122-5p inhibited EMT through downregulation of CCNG1. Overexpression of miR-122-5p could inhibit cell proliferation, migration, invasion, and EMT by downregulating CCNG1 in PDAC, suggesting a potential therapeutic target for PDAC.

中文翻译：

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MicroRNA-122-5p通过靶向CCNG1抑制胰腺导管腺癌中的细胞增殖、迁移和侵袭

胰腺导管腺癌 (PDAC) 是一种致命的人类恶性肿瘤，先前的研究支持 microRNA (miRNA) 对癌症进展的贡献。据报道，miR-122-5p 参与多种癌症的调节，而 miR-122-5p 在 PDAC 中的功能仍不清楚。在这项研究中，我们研究了 miR-122-5p 参与 PDAC 发病机制的确切机制。通过miRNA RT-PCR检测人PDAC组织和细胞系中miR-122-5p的表达水平。通过 MTT 测定、集落形成测定和流式细胞术测定探索 miR-122-5p 对细胞增殖的影响。迁移和侵袭的能力由transwell 测定法确定。进行双荧光素酶报告基因测定以验证 miR-122-5p 与其靶基因之间的直接相互作用。细胞周期的相关分子，用qRT-PCR和蛋白质印迹检查细胞凋亡和上皮 - 间质转化（EMT）。此外，应用异种移植小鼠模型来探索 miR-122-5p 在体内的作用。MiR-122-5p 低表达，而 CCNG1 在 PDAC 组织和细胞中高表达。MiR-122-5p与PDAC患者的TNM分期、肿瘤大小和淋巴结转移呈负相关。miR-122-5p的过表达在体外抑制增殖、迁移和侵袭，在体内抑制肿瘤发生。此外，CCNG1 是 miR-122-5p 的直接靶标。上调的 CCNG1 可以部分逆转 miR-122-5p 引起的影响。此外，miR-122-5p 通过下调 CCNG1 抑制 EMT。过表达 miR-122-5p 可通过下调 PDAC 中的 CCNG1 抑制细胞增殖、迁移、侵袭和 EMT，