Dai Chen, Zhang Yan, Xu Zhihua, Jin Mengxian
2Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, 215006 China.
3Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, 215006 China.
Cancer Cell Int. 2020 Mar 30;20:98. doi: 10.1186/s12935-020-01185-z. eCollection 2020.
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.
胰腺导管腺癌（PDAC）是一种致命的人类恶性肿瘤，先前的研究支持微小RNA（miRNA）对癌症进展的作用。据报道，miR-122-5p参与多种癌症的调控，而其在PDAC中的功能仍不清楚。在本研究中，我们探讨了miR-122-5p参与PDAC发病机制的精确机制。
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法、集落形成试验和流式细胞术试验探讨miR-122-5p对细胞增殖的影响。通过Transwell试验测定迁移和侵袭能力。进行双荧光素酶报告基因试验以验证miR-122-5p与其靶基因之间的直接相互作用。用qRT-PCR和western blot检测细胞周期、凋亡和上皮-间质转化（EMT）的相关分子。此外，应用异种移植小鼠模型探讨miR-122-5p在体内的作用。
miR-122-5p在PDAC组织和细胞中低表达，而CCNG1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了增殖、迁移和侵袭，并在体内抑制了肿瘤发生。此外，CCNG1是miR-122-5p的直接靶标。上调CCNG1可部分逆转miR-122-5p引起的效应。此外，miR-122-5p通过下调CCNG1抑制EMT。
miR-122-5p的过表达可通过下调PDAC中的CCNG1抑制细胞增殖、迁移、侵袭和EMT，提示其可能是PDAC的治疗靶点。
