Department of Hepatobiliary Surgery, Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of ZheJiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of ZheJiang Province, Center of Precision Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
Front Immunol. 2019 Dec 11;10:2819. doi: 10.3389/fimmu.2019.02819. eCollection 2019.
Increasing evidences have suggested that natural killer (NK) cells in the tumor microenvironment are involved in the regulation of cancer development. However, the potential biological roles and regulatory mechanisms of NK cells in pancreatic cancer (PC) remain unclear. Co-culture system of NK cells with PC cells is used to test the ability of cancer cell proliferation, migration and invasion both and . And tail vein intravenous transfer was used to test metastasis . Meanwhile, extracellular vesicles (EVs) were separated and examined. Furthermore, reporter assay and Biotin-RNA pull down assay were performed to verify the interaction between molecules. NK cells can inhibit the malignant transformation of co-cultured PC cells both and , which requires miR-3607-3p. miR-3607-3p is found enriched in the EVs of NK cells and transmitted to PC cells, and low level of miR-3607-3p predicts poor prognosis in PC patients. It can also inhibit proliferation, migration and invasion of PC cells . Importantly, IL-26 is found to be a direct target of miR-3607-3p in PC cells. miR-3607-3p enriched in EVs derived from NK cells can inhibit the malignant transformation of PC probably through directly targeting of IL-26.
越来越多的证据表明，肿瘤微环境中的自然杀伤 (NK) 细胞参与了癌症的发展调控。然而，NK 细胞在胰腺癌 (PC) 中的潜在生物学作用和调节机制仍不清楚。NK 细胞与 PC 细胞共培养系统用于测试癌细胞增殖、迁移和侵袭的能力。并且通过尾静脉静脉内转移来测试转移。同时，分离并检查细胞外囊泡 (EVs)。此外，进行了报告基因检测和生物素-RNA 下拉检测以验证分子之间的相互作用。NK 细胞可以抑制共培养的 PC 细胞的恶性转化，这需要 miR-3607-3p。miR-3607-3p 在 NK 细胞的 EVs 中富集并传递到 PC 细胞中，低水平的 miR-3607-3p预示着 PC 患者预后不良。它还可以抑制 PC 细胞的增殖、迁移和侵袭。重要的是，发现 IL-26 是 PC 细胞中 miR-3607-3p 的直接靶标。来自 NK 细胞的 EVs 中富集的 miR-3607-3p 可能通过直接靶向 IL-26 来抑制 PC 的恶性转化。
