Crucial role of miR-31 in induction of CD8+ T-cell exhaustion and reinforcement of type 1 interferon signaling

Li, Lin Ying; Hwang, Inkyu

doi:10.1038/cmi.2017.96

Cited by 1 publication

(1 citation statement)

References 7 publications

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“…Moreover, TGF-β induced expressions of miR-17, miR-23a, miR-31, miR-145 and miR-181a at levels of cellular and exosomal in A549 cells, suggesting that these miRNAs play crucial roles in both TGF-β-induced aggressiveness phonotype and modulation of microenvironment in lung cancers. Eventually, this study suggests that exosomal miRNAs derived from TGF-β-induced tumor cells could be a potent vehicle for defence mechanism against immune response 3,[19][20][21][22][23][24][25][26][27][28][29] .…”

Section: Introductionmentioning

confidence: 87%

Transforming Growth Factor-Beta (TGF-β) Employs Epithelial-Mesenchymal Transition (EMT)-Inducible Cancer Cells to Secrete the Exosomal miRNAs Regulating the Immune Response

Kucuksayan¹,

Kucuksayan²

2021

jamp

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Epithelial-mesenchymal transition (EMT) is a vital program required for cancer invasion and metastasis. EMT inducer transforming growth factor-beta (TGF-β) is implicated in carcinogenesis by contributing metastasis, immune evasion, and immunosuppression. Cancer cells employ different mechanisms to suppress the differentiation and the activation of immune system cells. Recent studies have reported that exosomes derived from cancer cells induced by several internal and external factors may suppress the immune system. We aimed to illustrate whether TGF-β recruits cancer cells to secrete several miRNAs that could suppress the immune system. We performed all experiments with TGF-β-responsive (A549) non-small cell lung cancer and (PANC-1) pancreatic ductal adenocarcinoma cell lines used as in vitro models. We isolated exosomes secreted by TGF-β-induced cells. We analyzed miRNAs in exosomes by qPCR. We showed that miR-1246 was significantly increased in exosomes secreted by TGF-β-induced A549 cells, indicating that miR-1246 upregulation could contribute to exosome-mediated immunosuppression in lung cancer patients. Also, TGF-β upregulated expression levels of miR-17, miR-23a, miR-31, miR-145 and miR-181a as cellular and exosomal in A549 cells. Interestingly, TGF-β selectively induced exosomal miR-150 expression in A549 cells, suggesting that lung cancer cells might secrete exosomal miR-150 to suppress immune cells. Conversely, we observed that PANC-1 cells display reticent behaviour to secrete exosomal miRNAs in response to TGF-β treatment compared to A549 cells. Our study reveals that TGF-β selectively might regulate the expression of exosomal miRNAs in especially lung cancer cells. So, this study will contribute to further studies with lung cancer patients

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