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Exosomes with low miR-34c-3p expression promote invasion and migration of non-small cell lung cancer by upregulating integrin ?2?1.

ABSTRACT: Exosomes play critical roles in regulating various physiological and pathological processes, including immune stimulation, immune suppression, cardiovascular diseases, and cancers. Recent studies show that exosomes that transport specific microRNAs (miRNAs) are involved in tumor development. However, the molecular mechanism by which tumor invasion and migration are regulated by exosomes from non-small cell lung cancer (NSCLC) is not well understood. Here, we show that exosomes shuttling low levels of miR-34c-3p are involved in NSCLC progression. Our results showed that exosomes derived from NSCLC cells carrying low levels of miR-34c-3p could be transported into the cytoplasm of NSCLC cells and accelerate NSCLC invasion and migration by upregulating integrin ?2?1. A luciferase assay revealed that integrin ?2?1 was the direct target of miR-34c-3p, and overexpression of integrin ?2?1 could promote the invasion and migration of NSCLC cells. The analysis of exosomes derived from clinical serum samples indicated that the expression of miR-34c-3p was significantly downregulated in exosomes from NSCLC patients compared with that of normal controls. A549-derived exosomes promoted NSCLC cells lung metastases in vivo. Exosomes shuttling low levels of miR-34c-3p were associated with the progression of NSCLC in vitro and in vivo. Our data demonstrate that exosomes shuttling low levels of miR-34c-3p can accelerate the invasion and migration of NSCLC by upregulating integrin ?2?1. MiR-34c-3p can be a diagnostic and prognostic marker for NSCLC. High expression of integrin ?2?1 is positively related to the migration and metastasis of NSCLC cells.

SUBMITTER: Huang W

PROVIDER: S-EPMC7174429 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Exosomes with low miR-34c-3p expression promote invasion and migration of non-small cell lung cancer by upregulating integrin α2β1.

Huang Wenjing W Yan Yanyan Y Liu Yun Y Lin Minting M Ma Jinxiang J Zhang Wei W Dai Jianwei J Li Jiajun J Guo Qiaoru Q Chen Hubiao H Makabel Bolat B Liu Hong H Su Chaoyue C Bi Hong H Zhang Jianye J

Signal transduction and targeted therapy 20200422 1

Exosomes play critical roles in regulating various physiological and pathological processes, including immune stimulation, immune suppression, cardiovascular diseases, and cancers. Recent studies show that exosomes that transport specific microRNAs (miRNAs) are involved in tumor development. However, the molecular mechanism by which tumor invasion and migration are regulated by exosomes from non-small cell lung cancer (NSCLC) is not well understood. Here, we show that exosomes shuttling low leve ...[more]

PMID: 32317629

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Project description:BackgroundEmerging evidence has revealed that tumor-associated macrophages (TAMs) and exosomes play a crucial role in the microenvironment for tumor growth. However, the mechanisms through which exosomal miRNAs modulate TAMs and tumor development in breast cancer are not fully understood.MethodsWe constructed a macrophage model and an indirect coculture system consist of breast cancer cells and macrophages. Exosomes were isolated from BC cells culture supernatant and identified by transmission electron microscopy, Western blot and Nanosight LM10 system. The expression of miR-148b-3p in exosomes was determined by qRT-PCR and the effect of exosomal miR-148b-3p on macrophage polarization was measured using qRT-PCR and ELISA. The proliferation, migration and invasion of BC cells were estimated by EdU, wound healing assay and transwell assay. We employed bioinformatics, luciferase reporter assay and Western blot to identify the target gene of miR-148b-3p. Western blot was used to clarify the mechanism of exosomal miR-148b-3p mediated the crosstalk between BC cells and M2 macrophages.ResultsCancer-derived exosomes could induce M2 polarization of macrophages, which promoted the migration and invasion of breast cancer cells. We found that exosomal miR-148b-3p was overexpressed in breast cancer cell-derived exosomes and correlated with lymph node metastasis, late tumor stage and worse prognosis. Upregulated miR-148b-3p expression in exosomes modulated macrophage polarization by targeting TSC2, which promoted the proliferation and might affect migration and invasion of breast cancer cells. Interestingly, we found that exosomal miR-148b-3p could induce M2 macrophage polarization via the TSC2/mTORC1 signaling pathway in breast cancer.ConclusionOverall, our study elucidated that miR-148b-3p could be transported by exosomes from breast cancer cells to surrounding macrophages and induced M2 polarization by targeting TSC2, providing novel insights for breast cancer therapy.

Dataset Information

Exosomes with low miR-34c-3p expression promote invasion and migration of non-small cell lung cancer by upregulating integrin ?2?1.

Publications

Exosomes with low miR-34c-3p expression promote invasion and migration of non-small cell lung cancer by upregulating integrin α2β1.

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