Open AccessIdentification of extracellular vesicles‐transported miRNAs in Erlotinib‐resistant head and neck squamous cell carcinoma
Author(s) -
Zheng Yang,
Song An,
Zhou Yan,
Zhong Yi,
Zhang Wei,
Wang Chundi,
Ding Xu,
Du Yifei,
Zhang Wei,
Li Gang,
Wu Heming,
Wu Yug,
Song Xiaomeng
Publication year - 2020
Publication title -
journal of cell communication and signaling
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 44
eISSN - 1873-961X
pISSN - 1873-9601
DOI - 10.1007/s12079-020-00546-7
Subject(s) - erlotinib , head and neck squamous cell carcinoma , microrna , transfection , cancer research , epidermal growth factor receptor , medicine , western blot , extracellular vesicles , biology , cell culture , cancer , head and neck cancer , microbiology and biotechnology , gene , biochemistry , genetics
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.