State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat‑sen University Cancer Center, Guangzhou, Guangdong 510060, P.R. China.
Department of Endocrinology, People's Hospital of Xinjiang Uyghur Autonomous Region, Urumqi, Xinjiang 830063, P.R. China.
Oncol Rep. 2018 Nov;40(5):2750-2757. doi: 10.3892/or.2018.6642. Epub 2018 Aug 10.
Deregulated microRNAs play an important role in the development and progression of various types of cancer. In our previous study, we observed that microRNA‑342‑3p (miR‑342‑3p) was one of the most markedly downregulated microRNAs in two nasopharyngeal carcinoma (NPC) cell lines compared to non‑neoplastic cells by using whole genome small RNA sequencing. In the present study, we confirmed that the expression of miR‑342‑3p was significantly reduced in NPC tissues compared with normal nasopharyngeal epithelial tissues. Overexpression of miR‑342‑3p inhibited proliferation, epithelial‑mesenchymal transition (EMT), migration and invasiveness of NPC cells. In addition, we observed that Cdc42, a Rho GTPase family member involved in cell proliferation and metastasis, is a direct target of miR‑342‑3p. Additionally, ML141, a small‑molecule inhibitor of Cdc42, efficiently suppressed the invasion of NPC cells compared with the control cells. Finally, we analyzed NPC tissues derived from 10 NPC patients and subjected them to quantitative RT‑PCR and immunohistochemistry assays for concomitant determination of the expression levels of miR‑342‑3p and Cdc42. Our results revealed that miR‑342‑3p levels were significantly inversely correlated with the protein levels of its target Cdc42. The results of the present study indicated that miR‑342‑3p inhibited NPC tumor growth and invasion by directly targeting the Cdc42 pathway.
失调的 microRNAs 在各种类型癌症的发展和进展中发挥着重要作用。在我们之前的研究中，我们通过全基因组小 RNA 测序观察到，与非肿瘤细胞相比，两种鼻咽癌（NPC）细胞系中 microRNA-342-3p（miR-342-3p）是下调最明显的 microRNA 之一。在本研究中，我们证实与正常鼻咽上皮组织相比，NPC 组织中 miR-342-3p 的表达显著降低。miR-342-3p 的过表达抑制 NPC 细胞的增殖、上皮-间充质转化（EMT）、迁移和侵袭。此外，我们观察到 Cdc42 是一种参与细胞增殖和转移的 Rho GTPase 家族成员，是 miR-342-3p 的直接靶标。此外，Cdc42 的小分子抑制剂 ML141 与对照细胞相比，能有效抑制 NPC 细胞的侵袭。最后，我们分析了来自 10 名 NPC 患者的 NPC 组织，并对其进行了定量 RT-PCR 和免疫组织化学检测，以同时测定 miR-342-3p 和 Cdc42 的表达水平。我们的结果表明 miR-342-3p 的水平与 Cdc42 靶蛋白的水平呈显著负相关。本研究结果表明，miR-342-3p 通过直接靶向 Cdc42 通路抑制 NPC 肿瘤的生长和侵袭。
