Department of Neurosurgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing 100032, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4049-4056. doi: 10.3892/mmr.2017.8361. Epub 2017 Dec 27.
Numerous microRNAs (miRNAs) are aberrantly expressed in glioma, and implicated in glioma occurrence and development. Therefore, the development of miRNAs as potential therapeutic targets for the treatment of patients with glioma has been proposed. miR‑379 has been shown to be aberrantly expressed in the progression of malignant tumours. However, the expression, biological functions and mechanism of miR‑379 in glioma are yet to be fully understood. Hence, the present study aimed to detect miR‑379 expression, investigate its functional relevance and explore its associated molecular mechanism in glioma. In this study, miR‑379 expression was significantly downregulated in glioma tissues and cell lines. Enforced miR‑379 expression markedly suppressed the cell proliferation and invasion of glioma. Metadherin (MTDH) was identified as a direct target of miR‑379 in glioma. The miR‑379 expression and MTDH mRNA levels exhibited an inverse association in glioma tissues. The restoration of the MTDH expression partially rescued the inhibitory effects of miR‑379 overexpression on glioma cell proliferation and invasion, and the upregulation of miR‑379 inhibited the activation of phosphatase and tensin homolog (PTEN)/AKT serine/threonine kinase (AKT) signaling pathway. Overall, these findings demonstrated that miR‑379 may play tumour‑suppressing roles in glioma through downregulation of MTDH and regulation of the PTEN/AKT signaling pathway, suggesting that miR‑379 might be a possible target for the treatment of patients with this malignancy.
许多 microRNAs（miRNAs）在神经胶质瘤中表达异常，并与神经胶质瘤的发生和发展有关。因此，已经提出将 miRNAs 作为治疗神经胶质瘤患者的潜在治疗靶点进行开发。miR-379 在恶性肿瘤的进展中表达异常。然而，miR-379 在神经胶质瘤中的表达、生物学功能和机制尚未完全了解。因此，本研究旨在检测 miR-379 的表达，研究其功能相关性，并探讨其在神经胶质瘤中的相关分子机制。在这项研究中，miR-379 的表达在神经胶质瘤组织和细胞系中显著下调。过表达 miR-379 可显著抑制神经胶质瘤的细胞增殖和侵袭。在神经胶质瘤中，MTDH（metadherin）被鉴定为 miR-379 的直接靶基因。miR-379 的表达与神经胶质瘤组织中 MTDH mRNA 水平呈负相关。MTDH 表达的恢复部分挽救了 miR-379 过表达对神经胶质瘤细胞增殖和侵袭的抑制作用，上调 miR-379 抑制了磷酸酶和张力蛋白同源物（PTEN）/丝氨酸/苏氨酸激酶（AKT）信号通路的激活。综上所述，这些发现表明 miR-379 可能通过下调 MTDH 和调节 PTEN/AKT 信号通路在神经胶质瘤中发挥抑癌作用，提示 miR-379 可能是治疗这种恶性肿瘤的潜在靶点。
