M2 macrophage-derived exosomal microRNAs inhibit cell migration and invasion in gliomas through PI3K/AKT/mTOR signaling pathway
Authors: Zhiqiang Li
Chao Ma
Yahua Zhong
Zefen Wang
Jie Yao
Yong Cheng
Yilei Xiao
Xu Gao
Journal: Journal of Translational Medicine (2021)
Discipline: CLINICAL MEDICINE
Keywords: Exosome; Glioma; M2 macrophage; PI3K/AKT/mTOR; hsa-miR-15a-5p
Affiliations: Human Genetic Resources Conservation Center of Hubei Province, Wuhan, 430071, China., Tumor Precision Diagnosis and Treatment Technology and Translation Medicine, Hubei Engineering Research Center, Wuhan, 430071, China., Department of Physiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China., Department of Neurology, Hankou Hospital, General Hospital of Central Theater Command of Chinese People's Liberation Army, Wuhan, 430014, China., Department of Neurosurgery, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuhan, 430071, Hubei, China., Department of Oncology, Zhongnan Hospital of Wuhan University, Wuhan, 430071, China., Department of Neurosurgery, Liaocheng People's Hospital, Liaocheng, 252000, China., Department of Neurosurgery, General Hospital of Northern Theater Command of People's Liberation Army, Shenyang, 110000, China., Department of Neurosurgery, Zhongnan Hospital of Wuhan University, No 169 Donghu Road, Wuhan, 430071, Hubei, China. .

Abstract:  Background: Glioma, the most common primary brain tumor, account Preparing figures for 30 to 40% of all intracranial tumors. Herein, we aimed to study the effects of M2 macrophage-derived exosomal microRNAs (miRNAs) on glioma cells. Methods: First, we identified seven differentially expressed miRNAs in infiltrating macrophages and detected the expression of these seven miRNAs in M2 macrophages. We then selected hsa-miR-15a-5p (miR-15a) and hsa-miR-92a-3p (miR-92a) for follow-up studies, and confirmed that miR-15a and miR-92a were under-expressed in M2 macrophage exosomes. Subsequently, we demonstrated that M2 macrophage-derived exosomes promoted migration and invasion of glioma cells, while exosomal miR-15a and miR-92a had the opposite effects on glioma cells. Next, we performed the target gene prediction in four databases and conducted target gene validation by qRT-PCR, western blot and dual luciferase reporter gene assays. Results: The results revealed that miR-15a and miR-92a were bound to CCND1 and RAP1B, respectively. Western blot assays demonstrated that interference with the expression of CCND1 or RAP1B reduced the phosphorylation level of AKT and mTOR, indicating that both CCND1 and RAP1B can activate the PI3K/AKT/mTOR signaling pathway. Conclusion: Collectively, these findings indicate that M2 macrophage-derived exosomal miR-15a and miR-92a inhibit cell migration and invasion of glioma cells through PI3K/AKT/mTOR signaling pathway. 

Retracted: No

PubPeer comments:
 Figure 3d and 3d seem to have images which overlap, after some resizing. Some same authors as [this paper] , recently retracted for similar issues. *** ![file] , 
 Published: 16 June 2021 In the original publication [1] there was an error in Fig. 3. In the experiments every sample was shot from many different visual fields. However, due to human error a wrong figure with the same group of different visual field was uploaded. In this correction article the correct (Fig. 1) and incorrect (Fig. 2) version of Fig. 3 are published. The full captions are available via the original article. The original article has been updated. ![file] , 
 It appears that an image in the right panel of Figure 2b and an image in left panel of Figure 3c (as corrected) overlap, although the color and contrast appear different. Unclear why these differences would result during figure assembly. *** ![file] , 
 There appears to be two duplicated images in the right panels of both Figure 2b and 3c as noted below. *** ![file] , 
 Two images in the corrected Figure 3c appear to overlap, again with significant differences in coloring and contrast. *** ![file] *** Funding. The support in this work was from National Natural Science Foundation of China (81573459), Medical Science Advancement Program of Wuhan University (NO.TFJC2018003), and National Health Commission (2018ZX-07S-011). ,