MiRNAs correlate with HLA expression in uveal melanoma: Both up-and downregulation are related to monosomy 3

Zahra Souri, Annemijn P.A. Wierenga, Emine Kiliç, Erwin Brosens, Stefan Böhringer, Wilma G.M. Kroes, Robert M. Verdijk, Pieter A. van der Velden, Gregorius P.M. Luyten, Martine J. Jager*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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MicroRNAs are known to play a role in the regulation of inflammation. As a high HLA Class I expression is associated with a bad prognosis in UM, we set out to determine whether any miRNAs were related to a high HLA Class I expression and inflammation. We also determined whether such miRNAs were related to the UM’s genetic status. The expression of 125 miRNAs was determined in 64 primary UM from Leiden. Similarly, the mRNA expression of HLA-A, HLA-B, TAP1, BAP1, and immune cell markers was obtained. Expression levels of 24 of the 125 miRNAs correlated with expression of at least three out of four HLA Class I probes. Four miRNAs showed a positive correlation with HLA expression and infiltration with leukocytes, 20 a negative pattern. In the first group, high miRNA levels correlated with chromosome 3 loss/reduced BAP1 mRNA expression, in the second group low miRNA levels. The positive associations between miRNA- 22 and miRNA-155 with HLA Class I were confirmed in the TCGA study and Rotterdam cohort, and with TAP1 in the Rotterdam data set; the negative associations between miRNA-125b2 and miRNA-211 and HLA-A, TAP1, and CD4 were confirmed in the Rotterdam set. We demonstrate two patterns: miRNAs can either be related to a high or a low HLA Class I/TAP1 expression and the presence of infiltrating lymphocytes and macrophages. However, both patterns were associated with chromosome 3/BAP1 status, which suggests a role for BAP1 loss in the regulation of HLA expressionand inflammation in UM through miRNAs.

Original languageEnglish
Article number4020
Issue number16
Publication statusPublished - 10 Aug 2021

Bibliographical note

Funding Information:
Funding: This research was funded by a grant to Z.S. from The Iranian Ministry of Science Research and Technology, Grant UL 2011-4991 from the Dutch Cancer Society (KWF), Stichting Leids Oogheelkundig Ondersteunings Fonds, the Nelly Reef Fund, Family G., Ms. Brouwer and a Horizon 2020 grant from the European Community, CURE UM, nr. 667787.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.


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