Circulating microRNA-155-3p levels predicts response to first line immunotherapy in patients with metastatic renal cell carcinoma

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Abstract

Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment (TME) and the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties. We evaluated the presence of immune-specific extracellular vesicle (EV) microRNAs in the plasma of patients with metastatic RCC (mRCC) prior to initiation of ICI. We found significantly lower levels of microRNA155-3p (miR155) in responders to ICI, when compared to non-responders. This microRNA has unique immunomodulatory properties, thus providing potential biological rationale for our findings. Our results support further work in exploring microRNAs as potential biomarkers of response to immunotherapy.

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Most cited references 46

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Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

Hadi Valadi, Karin Ekström, Apostolos Bossios … (2007)

Exosomes are vesicles of endocytic origin released by many cells. These vesicles can mediate communication between cells, facilitating processes such as antigen presentation. Here, we show that exosomes from a mouse and a human mast cell line (MC/9 and HMC-1, respectively), as well as primary bone marrow-derived mouse mast cells, contain RNA. Microarray assessments revealed the presence of mRNA from approximately 1300 genes, many of which are not present in the cytoplasm of the donor cell. In vitro translation proved that the exosome mRNAs were functional. Quality control RNA analysis of total RNA derived from exosomes also revealed presence of small RNAs, including microRNAs. The RNA from mast cell exosomes is transferable to other mouse and human mast cells. After transfer of mouse exosomal RNA to human mast cells, new mouse proteins were found in the recipient cells, indicating that transferred exosomal mRNA can be translated after entering another cell. In summary, we show that exosomes contain both mRNA and microRNA, which can be delivered to another cell, and can be functional in this new location. We propose that this RNA is called "exosomal shuttle RNA" (esRNA).

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Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

Jacob O'Brien, Heyam Hayder, Yara Zayed … (2018)

MicroRNAs (miRNAs) are a class of non-coding RNAs that play important roles in regulating gene expression. The majority of miRNAs are transcribed from DNA sequences into primary miRNAs and processed into precursor miRNAs, and finally mature miRNAs. In most cases, miRNAs interact with the 3′ untranslated region (3′ UTR) of target mRNAs to induce mRNA degradation and translational repression. However, interaction of miRNAs with other regions, including the 5′ UTR, coding sequence, and gene promoters, have also been reported. Under certain conditions, miRNAs can also activate translation or regulate transcription. The interaction of miRNAs with their target genes is dynamic and dependent on many factors, such as subcellular location of miRNAs, the abundancy of miRNAs and target mRNAs, and the affinity of miRNA-mRNA interactions. miRNAs can be secreted into extracellular fluids and transported to target cells via vesicles, such as exosomes, or by binding to proteins, including Argonautes. Extracellular miRNAs function as chemical messengers to mediate cell-cell communication. In this review, we provide an update on canonical and non-canonical miRNA biogenesis pathways and various mechanisms underlying miRNA-mediated gene regulations. We also summarize the current knowledge of the dynamics of miRNA action and of the secretion, transfer, and uptake of extracellular miRNAs.

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miRBase: from microRNA sequences to function

Ana Kozomara, Maria Birgaoanu, Sam Griffiths-Jones (2018)

Abstract miRBase catalogs, names and distributes microRNA gene sequences. The latest release of miRBase (v22) contains microRNA sequences from 271 organisms: 38 589 hairpin precursors and 48 860 mature microRNAs. We describe improvements to the database and website to provide more information about the quality of microRNA gene annotations, and the cellular functions of their products. We have collected 1493 small RNA deep sequencing datasets and mapped a total of 5.5 billion reads to microRNA sequences. The read mapping patterns provide strong support for the validity of between 20% and 65% of microRNA annotations in different well-studied animal genomes, and evidence for the removal of >200 sequences from the database. To improve the availability of microRNA functional information, we are disseminating Gene Ontology terms annotated against miRBase sequences. We have also used a text-mining approach to search for microRNA gene names in the full-text of open access articles. Over 500 000 sentences from 18 542 papers contain microRNA names. We score these sentences for functional information and link them with 12 519 microRNA entries. The sentences themselves, and word clouds built from them, provide effective summaries of the functional information about specific microRNAs. miRBase is publicly and freely available at http://mirbase.org/.

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Author and article information

Contributors

Lucia Nappi: lucia.nappi@bccancer.bc.ca

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 13 April 2024

Publication date PMC-release: 13 April 2024

Publication date Collection: 2024

Volume: 14

Electronic Location Identifier: 8603

Affiliations

[1 ]GRID grid.248762.d, ISNI 0000 0001 0702 3000, Division of Medical Oncology, , British Columbia Cancer-Vancouver Cancer Centre, ; 600 West 10th Avenue, Vancouver, BC V5Z 4E6 Canada

[2 ]Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, University of Auckland, ( https://ror.org/03b94tp07) Auckland, New Zealand

[3 ]Vancouver Prostate Centre, Department of Urologic Sciences, University of British Columbia, ( https://ror.org/03rmrcq20) Vancouver, BC Canada

[4 ]Department of Cancer Immunology, Poznan University of Medical Sciences, ( https://ror.org/02zbb2597) Poznan, Poland

Article

Publisher ID: 59337

DOI: 10.1038/s41598-024-59337-4

PMC ID: 11016103

PubMed ID: 38615118

SO-VID: e8149876-2f19-4936-9d4c-82b23649948a

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 28 November 2023

Date accepted : 9 April 2024

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ScienceOpen disciplines: Uncategorized

Keywords: tumour biomarkers,predictive markers,renal cell carcinoma

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ScienceOpen disciplines: Uncategorized

Keywords: tumour biomarkers, predictive markers, renal cell carcinoma

Circulating microRNA-155-3p levels predicts response to first line immunotherapy in patients with metastatic renal cell carcinoma

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Abstract

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Cancer Immunotherapy

Most cited references 46

Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells.

Overview of MicroRNA Biogenesis, Mechanisms of Actions, and Circulation

miRBase: from microRNA sequences to function

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