MicroRNA‐193a‐5p exerts a tumor suppressor role in glioblastoma via modulating NOVA1
Authors: Gaojun Lin
Xiaowei Ying
Da Lin
Lingfang Teng
Zheng Lin
Ligang Lin
Huiyong Li
Kang Yin
Junyou Wang
Yongqiang Zhang
Lisong Wang
Lingjiang Jin
Hui Wang
Journal: Journal of Cellular Biochemistry (2019)
Discipline: MOLECULAR BIOLOGY & GENETICS
Keywords: disease-free survival; glioblastoma; invasion; miR-193a-5p; neuro-oncological ventral antigen 1
Affiliations: Department of Neurosurgery The Affiliated Wenling Hospital of Wenzhou Medical University Wenling China, The Center for Cerebrovascular Disease The Affiliated Wenling Hospital of Wenzhou Medical University Wenling China

Abstract:  Background and objectives: Glioblastoma (GBM) is the most common and lethal of intracranial tumors, which is characterized by extensive proliferation and the diffused invasion of tumor cells. MicroRNA-193a-5p (miR-193a-5p) have been demonstrated previously as a functional suppressor in the development and progression of various cancers. The current study aimed to investigate whether miR-193a-5p influences cell proliferation and migration through the mitogen-activated protein kinase/extracellular signal-regulated kinase signaling pathway by targeting neuro-oncological ventral antigen 1 (NOVA1) in glioblastoma. Materials and methods: The miR-193a-5p expression was detected by quantitative real-time polymerase chain reaction assay in GBM tissues and cell lines. Cell Counting Kit-8 assay, colony formation analysis, wound-healing, and transwell invasion assays were performed to evaluate cell proliferation, colony formation, migration, and invasion, respectively. Western blot analysis and luciferase reporter gene assay were performed to verify the downstream target gene of miR-193a-5p. Results: The expression of miR-193a-5p was significantly downregulated in GBM tissues and cell lines. Kaplan-Meier analysis showed that patients with low miR-193a-5p expression had a shorter disease-free survival (P &lt; 0.05). Functionally, miR-193a-5p overexpression dramatically suppressed the proliferation, colony formation, migration, and invasion in glioma cells. Bioinformatics prediction and a luciferase assay confirmed that NOVA1 was a direct functional target of miR-193a-5p. Moreover, ectopic expression of NOVA1 could partially reverse the inhibitory effects of miR-193a-5p on glioma cell proliferation, colony formation, migration, and invasion. NOVA1 overexpression abrogated the inhibitory effect of miR-193a-5p on the PTEN/PI3k/AKT pathway. Conclusion: Taken together, our findings suggested that miR-193a-5p functions as a tumor suppressor in glioma cells by directly targeting NOVA1. 

Retracted: No

PubPeer comments:
 Fig 5.  Western blot detecting the effect of miRu2010193au20105p on the PTEN PI3K Akt signaling pathway. ![file] The bands (and specifically the loading control) appear to be drawn from a small concourse of WBs. Here is a montage I prepared earlier. ![] Clockwise from upper left: Fig 6B,  protein band graph , from  MicroRNA-374 Exerts Protective Effects by Inhibiting SP1 Through Activating the PI3K Akt Pathway in Rat Models of Myocardial Ischemia-Reperfusion After Sevoflurane Preconditioning ([Zhang et al 2018] ). Fig 4D,  GLP-1R and CREB proteins in the myocardium of mice in each group examined by western blotting , from  Suppression of Long Non-Coding RNA LINC00652 Restores Sevoflurane-Induced Cardioprotection Against Myocardial Ischemia-Reperfusion Injury by Targeting GLP-1R Through the cAMP PKA Pathway in Mice ([Zhang et al 2018] ). Fig. 6B,  ELISA and western blot analysis were applied to determine the miR- 495 expression and mRNA and protein expression of NLRP3, TNF-u03b1, IL-1u03b2, IL-18 and caspase-1 , from  MicroRNA-495 Ameliorates Cardiac Microvascular Endothelial Cell Injury and Inflammatory Reaction by Suppressing the NLRP3 Inflammasome Signaling Pathway ([Zhou et al 2018] ). Fig 6B,  WB images showing protein expression of different genes in each group , from  MicroRNA-27a Suppresses Detrusor Fibrosis in Streptozotocin-Induced Diabetic Rats by Targeting PRKAA2 Through the TGF-u03b21 Smad3 Signaling Pathway . ([Wu et al 2018] ). Fig 11E,  protein bands of each factor in ASMCs of asthma mice in each group detected by western blot analysis , from  MicroRNA-485 Modulates the TGF-u03b2 Smads Signaling Pathway in Chronic Asthmatic Mice by Targeting Smurf2 . ([Wang et al 2018] ). ,