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Identification of extracellular vesicles-transported miRNAs in Erlotinib-resistant head and neck squamous cell carcinoma.

Abstract：

:Erlotinib is an oral tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) pathway. Although our previous study has proved the efficacy of Erlotinib in head and neck squamous cell carcinoma (HNSCC), it has also demonstrated poor clinical response rates and disappointing results in clinical trials for HNSCC to date. In this study, we discovered elevated cell proliferation and invasion ability in erlotinib-resistant HNSCC cells. The contributions of miRNAs within extracellular vesicles (EVs) during the formation of chemoresistance were investigated in this study. Among up-regulated miRNAs in EVs derived from resistant cells, miR-7704, miR-21-5p and miR-3960 showed the most pro-tumorigenic alterations after transfection. Conversely, let-7i-5p, miR-619-5p and miR-30e-3p demonstrated tumor suppressive effects. By performing qRT-PCR and Western blot analysis, we found Vimentin played a pivotal role in modulating erlotinib resistance. Additionally, immune system was highlighted in the GO and KEGG analyses. Transfection of miR-7704, miR-21-5p significantly elevated CTLA-4 and LAG3 mRNA levels. Meanwhile, miR-3960 increased the relative mRNA expression of TIM3 in HNSCC cells. Transfection of let-7i-5p, miR-619-5p and miR-30e-3p decreased these checkpoint factors. To conclude, the present study described the roles of EVs-transmitted miRNAs on erlotinib resistance. Targeting the disregulated immune system could be the effective method to overcome erlotinib-resistance in HNSCC cells.

journal_name

J Cell Commun Signal

journal_title

Journal of cell communication and signaling

authors

Zheng Y,Song A,Zhou Y,Zhong Y,Zhang W,Wang C,Ding X,Du Y,Zhang W,Li G,Wu H,Wu Y,Song X

doi

10.1007/s12079-020-00546-7

subject

Has Abstract

pub_date

2020-12-01 00:00:00

pages

389-402

issue

4

eissn

1873-9601

issn

1873-961X

pii

10.1007/s12079-020-00546-7

journal_volume

14

pub_type

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