M2 macrophages\u2010derived exosomal microRNA-501-3p promotes the progression of lung cancer via targeting WD repeat domain 82

Jie Lei,Peng Chen,Na Zhang,Jianfei Zhu,Feng Zhang,Xiaoping Wang,Tao Jiang

doi:10.1186/s12935-021-01783-5

Jie Lei, Peng Chen + Show 5 more

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https://doi.org/10.1186/s12935-021-01783-5

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Abstract

BackgroundExosomes are known to transmit microRNAs (miRNAs) to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown. We aim to explore the role of exosomal miR-501-3p in LC development via targeting WD repeat domain 82 (WDR82).MethodsLung cancer tissue and normal tissue specimens were collected, in which tumor-associated macrophages (TAM) were measured by immunohistochemistry. M2 macrophages were induced and treated with altered miR-501-3p, and then the exosomes were extracted and identified. MiR-501-3p and WDR82 expression in LC tissues and cell liens was determined. The predictive role of miR-501-3p in prognosis of LC patients was assessed, and the proliferation, colony formation ability, invasion, migration and apoptosis of the LC cells were determined. Targeting relationship between miR-501-3p and WDR82 was confirmed.ResultsTAM level was elevated in lung cancer tissues. MiR-501-3p was upregulated while WDR82 was downregulated in LC tissues and cell lines, and the M2 exosomes further upregulated miR-501-3p. M2 exosomes and exosomal miR-501-3p promoted LC cell growth. MiR-501-3p inhibition reversed the effect of M2 exosomes on LC cells. WDR82 was confirmed as a target gene of miR-501-3p.ConclusionM2 macrophages-derived exosomal miR-501-3p promotes the progression of LC via downregulating WDR82.

Highlights

Exosomes are known to transmit microRNAs to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown
We aimed to investigate the role of M2 macrophages-derived exosomal miR-501-3p in the development of LC with the involvement of WD repeat domain 82 (WDR82), and we supposed that M2 exosomal miR-501-3p could affect LC progression by targeting WDR82
MiR‐501‐3p is upregulated while WDR82 is downregulated in LC tissues and cells, and high miR‐501‐3p expression is associated with a poor prognosis Firstly, miR-501-3p expression in LC patients was analyzed by starbase website, showing an increase in its level (Fig. 1a). miR-501-3p and WDR82 expression in tissues were assessed and we found that LC tissues had higher miR-501-3p expression and lower WDR82 expression versus adjacent normal tissues (Fig. 1b, c), and the Pearson test revealed that there existed a negative relationship between expression of miR-501-3p and WDR82 (Fig. 1d)

Summary

Introduction

Exosomes are known to transmit microRNAs (miRNAs) to affect cancer progression, while the role of M2 macrophages-derived exosomes (M2 exosomes) conveying miR-501-3p in lung cancer (LC) remains unknown. We aim to explore the role of exosomal miR-501-3p in LC development via targeting WD repeat domain 82 (WDR82). It has been reported that THP-1 macrophages activated by exosomes derived from lung adenocarcinoma cells promoted LC cell invasion [9]. M2 macrophages-derived exosomes (M2 exosomes) upregulated miR-501-3p to promotes progression of pancreatic ductal adenocarcinoma (PDAC) [17]. We aimed to investigate the role of M2 macrophages-derived exosomal miR-501-3p in the development of LC with the involvement of WDR82, and we supposed that M2 exosomal miR-501-3p could affect LC progression by targeting WDR82

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