Department of Neurosurgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Radiation Oncology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Rep. 2017 Aug;38(2):1240-1250. doi: 10.3892/or.2017.5783. Epub 2017 Jul 3.
Glioma is an extremely aggressive and lethal type of brain tumour that originates from glial cells. MicroRNA (miRNA) dysregulation has been implicated in the occurrence and progression of many human cancers, including glioma. Thus, some specific miRNAs are potential therapeutic targets for glioma diagnosis, therapy and prognosis. MicroRNA-342 (miR‑342) has been reported to be abnormally expressed in various types of cancer. However, the precise roles of miR‑342 in glioma remain unknown. The present study showed that miR‑342 is relatively downregulated in glioma tissues and cell lines compared with that in adjacent normal tissues and normal human astrocytes. We observed that low miR‑342 expression levels are correlated with advanced WHO grades and low KPS scores of glioma patients. In addition, the results of the functional assays demonstrated that miR‑342 overexpression inhibits the proliferation and invasion of glioma cells and induces apoptosis. Further investigation revealed that P21 activated kinases 4 (PAK4) is a direct target of miR‑342 in glioma. PAK4 was significantly upregulated in glioma tissues and inversely correlated with miR‑342 expression. Moreover, PAK4 knockdown can mimic the effects of miR‑342 on glioma cell proliferation, invasion and apoptosis. Notably, restoration of expression of PAK4 reversed the suppressive effects induced by the miR‑342 in the glioma cells. The upregulation of miR‑342 inactivated the AKT and ERK pathways in glioma. These findings may contribute to the understanding of the molecular mechanism underlying the carcinogenesis and progression of glioma, and to provide novel therapeutic target for the treatment of glioma patients.
神经胶质瘤是一种源自神经胶质细胞的极具侵袭性和致命性的脑肿瘤。MicroRNA（miRNA）失调与许多人类癌症的发生和进展有关，包括神经胶质瘤。因此，一些特定的miRNA可能是神经胶质瘤诊断、治疗和预后的潜在治疗靶点。MicroRNA-342（miR-342）已被报道在各种类型的癌症中异常表达。然而，miR-342 在神经胶质瘤中的确切作用仍不清楚。本研究表明，与相邻正常组织和正常人星形胶质细胞相比，miR-342 在神经胶质瘤组织和细胞系中相对下调。我们观察到低 miR-342 表达水平与神经胶质瘤患者的高级别 WHO 分级和低 KPS 评分相关。此外，功能测定的结果表明，miR-342 过表达抑制神经胶质瘤细胞的增殖和侵袭，并诱导细胞凋亡。进一步研究表明，P21 激活激酶 4（PAK4）是神经胶质瘤中 miR-342 的直接靶标。PAK4 在神经胶质瘤组织中明显上调，与 miR-342 表达呈负相关。此外，PAK4 敲低可模拟 miR-342 对神经胶质瘤细胞增殖、侵袭和凋亡的作用。值得注意的是，PAK4 的表达恢复逆转了 miR-342 在神经胶质瘤细胞中诱导的抑制作用。miR-342 的上调使神经胶质瘤中的 AKT 和 ERK 通路失活。这些发现可能有助于理解神经胶质瘤发生和进展的分子机制，并为神经胶质瘤患者的治疗提供新的治疗靶点。
