Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

Rachel Kerslake, Cristina Sisu, Suzana Panfilov, Marcia Hall, Nabeel Khan, Jeyarooban Jeyaneethi, Harpal Randeva, Ioannis Kyrou, Emmanouil Karteris

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    Abstract

    Background: Ovarian cancer (OvCa) is one of the most lethal forms of gynaecological malignancy. Altered energy metabolism and increased aerobic glycolysis in OvCa are hallmarks that demand attention. The glucogenic hormone asprosin is often dysregulated in metabolic disorders such as insulin resistance, diabetes (type 2 and gestational), and preeclampsia. Despite association with metabolic disorders, its role in energy metabolism within the tumour microenvironment is yet to be explored. Here, we study the role of asprosin in OvCa using transcriptomics and expand on functional studies with clinical samples. Methods: RNA sequencing, functional gene enrichment analysis, Western blotting and ImageStream. Results: Following treatment with 100 nM of asprosin, the serous OvCa cell line, SKOV-3, displayed 160 and 173 gene regulatory changes, at 4 and 12 h respectively, when compared with control samples (p < 0.05 and Log2FC > 1). In addition to energy metabolism and glucose-related pathways, asprosin was shown to alter pathways associated with cell communication, TGF-β signalling, and cell proliferation. Moreover, asprosin was shown to induce phosphorylation of ERK1/2 in the same in vitro model. Using liquid biopsies, we also report for novel expression of asprosin’s predicted receptors OR4M1 and TLR4 in cancer-associated circulating cells; with significant reduction seen between pre-chemotherapy and end of first line chemotherapy, in addition to patients under maintenance with bevacizumab +/− olaparib for OR4M1. Conclusions: In relation to OvCa, asprosin appears to regulate numerous signalling pathways in-vitro. The prognostic potential of OR4M1 in liquid biopsies should also be explored further.

    Original languageEnglish
    Article number5942
    Number of pages18
    JournalJournal of Clinical Medicine
    Volume11
    Issue number19
    DOIs
    Publication statusPublished - 8 Oct 2022

    Bibliographical note

    Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).

    Funder

    The present study was funded by Cancer Treatment & Research Trust (CTRT) and University Hospitals Coventry and Warwickshire NHS Trust (grant no. 12899).

    Keywords

    • asprosin
    • HGSC
    • high grade serous ovarian cancer
    • metabolism
    • OR4M1
    • ovarian cancer
    • OvCa
    • RNA sequencing
    • TLR4

    ASJC Scopus subject areas

    • Medicine(all)

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