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MiR-92 overexpression suppresses immune cell function in ovarian cancer via LATS2/YAP1/PD-L1 pathway

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Abstract

Purpose

Increasing evidence suggested that microRNA plays an important role in ovarian cancer. In this study, the role of miR-92 in ovarian cancer was investigated.

Methods

In this study, miR-92 expression in clinical sample was evaluated, role of miR-92 was investigated in vitro, and underlying mechanism was investigated using Chip, co-IP, and western blot.

Results

In this study, we show that miR-92 is overexpressed in ovarian cancer tissue compared with normal cancer tissue. Transfection of miR-92 increased proliferation of ovarian cancer cell, and increased migration capacity and colony formation were observed after miR-92 transfection; we found that expression of LATS2 was decreased by miR-92, and this was further confirmed by luciferase assay, which proved that miR-92 is targeting 3′ of the endogenous LATS2 gene. Downregulation of LATS2 resulted in increased translocation of YAP1 and upregulation of PD-L1, which subsequently suppressed NK cell function and promoted T cell apoptosis. Moreover, co-transfection of YAP1-targeted shRNA could relieve miR-92-induced immune suppression effect. Mechanically, immunoprecipitation (IP) was used to show that LATS2 interacted with YAP1 and subsequently limited nuclear translocation of YAP1; chromatin immunoprecipitation (ChIP) was used to confirm that YAP1 could bind to enhancer region of PD-L1 to enhance transcription activity of PD-L1.

Conclusions

Our data revealed a novel mechanism which finally resulted in immune suppression in ovarian cancer.

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Authors and Affiliations

Authors

Contributions

S.F. and W.Z. conceived and designed the study. S.F. and H.T. did the main experiments. S.F. analyzed and interpreted the data. H.T. was responsible for reagents and materials. S.F. drafted the article. W.Z. and H.T. revised the article critically. All authors had final approval of the submitted versions.

Corresponding author

Correspondence to W. Zhu.

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There are no conflicts of interest.

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This work has been approved by the ethical committees at Soochow University.

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All patients provided written informed consent.

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Feng, S., Sun, H. & Zhu, W. MiR-92 overexpression suppresses immune cell function in ovarian cancer via LATS2/YAP1/PD-L1 pathway. Clin Transl Oncol 23, 450–458 (2021). https://doi.org/10.1007/s12094-020-02439-y

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  • DOI: https://doi.org/10.1007/s12094-020-02439-y

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