MicroRNA-485 inhibits malignant biological behaviour of glioblastoma cells by directly targeting PAK4
Authors: Ding Lei
Heng Zhang
Ke Mao
Chao You
Journal: International Journal of Oncology (2017)
Discipline: CLINICAL MEDICINE
Keywords: Glioblastoma; MicroRNA; miR-485; PAK4; Tumour suppressor
Affiliations: Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, P.R. China.

Abstract:  Glioblastoma (GBM), which is characterised by rapid growth, cellular heterogeneity, angiogenesis, extensive invasion, hypoxia and necrosis, is the most common histological subtype of glioma in adults. MicroRNA (miRNA) dysregulation is a common feature of human cancers, including GBM. Previous studies have suggested that miRNAs are a novel class of regulatory molecules in various human cancers. Therefore, miRNAs may be investigated as a novel candidate and screening tool in the clinical diagnosis, therapy and prognosis of GBM. Recent accumulating evidence has demonstrated that miRNA‑485 (miR‑485) is involved in the development and progression of several types of human cancers. However, the expression level, exact role and underlying mechanisms of miR‑485 in GBM remain unclear. In this study, miR‑485 was downregulated in both GBM tissue specimens and cell lines. miR‑485 overexpression inhibited GBM cell proliferation, colony formation, migration and invasion; increased apoptosis in vitro; and reduced tumour growth in vivo. In addition, p21‑activated kinase 4 (PAK4) was demonstrated to be a direct and functional target of miR‑485 in GBM. Furthermore, PAK4 was upregulated in GBM tissues and negatively correlated with miR‑485 expression. Moreover, PAK4 knockdown exhibited a similar effect to miR‑485 overexpression in GBM cells. Enforced expression of PAK4 rescued miR‑485 tumour‑suppressor functions in GBM cells. miR‑485 inhibited the activation of the AKT and ERK signalling pathways in GBM. These results indicate that miR‑485 acts as a tumour suppressor in GBM by, at least partially, directly targeting PAK4 and regulating the AKT and ERK signalling pathways. Thus, miR‑485 may be a potential target for the treatment of patients with GBM. 

Retracted: No

PubPeer comments:
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 *[top]* Fig 2C from  MicroRNA-935 Inhibits Proliferation and Invasion of Osteosarcoma Cells by Directly Targeting High Mobility Group Box 1 ([Liu et al 2018] ). *[middle]* Fig 2C from  MicroRNA-655 attenuates the malignant biological behaviours of retinoblastoma cells by directly targeting PAX6 and suppressing the ERK and p38u00efu00bfu00bdMAPK signalling pathways ([Zhang et al 2018] ). *[bottom]* **Fig 3B**. ![] H t ImageTwin , 
 While we re at it: *[left]* Fig 5C from  MicroRNAu2011448 inhibits the progression of retinoblastoma by directly targeting ROCK1 and regulating PI3K AKT signalling pathway ([Wu et al 2018] . *[right]* **Fig 3A**. ![file] , 
 *[left]* Fig 5B from  MicroRNAu2011509 targets PAX6 to inhibit cell proliferation and invasion in papillary thyroid carcinoma ([Zhang et al 2018] ). *[upper right]* Fig 2C from  MicroRNAu2011598 inhibits the proliferation and invasion of nonu2011small cell lung cancer cells by directly targeting ZEB2 ([Tong et al 2018] ). *[lower right]* **Fig 7E F**. ![file] , 
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