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

doi:10.3390/cancers13164020

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 journal › Article › Academic › peer-review

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Abstract

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 language	English
Article number	4020
Journal	Cancers
Volume	13
Issue number	16
DOIs	https://doi.org/10.3390/cancers13164020
Publication status	Published - 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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cancers-13-04020-v3Final published version, 1.87 MBLicence: CC BY

Cite this

@article{5abbb42960514c849ee93be468219e71,

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

abstract = "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{\textquoteright}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.",

author = "Zahra Souri and Wierenga, {Annemijn P.A.} and Emine Kili{\c c} and Erwin Brosens and Stefan B{\"o}hringer and Kroes, {Wilma G.M.} and Verdijk, {Robert M.} and {van der Velden}, {Pieter A.} and Luyten, {Gregorius P.M.} and Jager, {Martine J.}",

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: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

month = aug,

day = "10",

doi = "10.3390/cancers13164020",

language = "English",

volume = "13",

journal = "Cancers",

issn = "2072-6694",

publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",

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TY - JOUR

T1 - MiRNAs correlate with HLA expression in uveal melanoma

T2 - Both up-and downregulation are related to monosomy 3

AU - Souri, Zahra

AU - Wierenga, Annemijn P.A.

AU - Kiliç, Emine

AU - Brosens, Erwin

AU - Böhringer, Stefan

AU - Kroes, Wilma G.M.

AU - Verdijk, Robert M.

AU - van der Velden, Pieter A.

AU - Luyten, Gregorius P.M.

AU - Jager, Martine J.

N1 - 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.

PY - 2021/8/10

Y1 - 2021/8/10

N2 - 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.

AB - 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.

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U2 - 10.3390/cancers13164020

DO - 10.3390/cancers13164020

M3 - Article

C2 - 34439175

AN - SCOPUS:85112255895

SN - 2072-6694

VL - 13

JO - Cancers

JF - Cancers

IS - 16

M1 - 4020

ER -

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

Abstract

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