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Differential regulation of genes by the glucogenic hormone asprosin in ovarian cancer
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Kerslake, Rachel, Sisu, Cristina, Panfilov, Suzana, Hall, Marcia, Khan, Nabeel, Jeyaneethi, Jeyarooban, Randeva, Harpal S., Kyrou, Ioannis and Karteris, Emmanouil (2022) Differential regulation of genes by the glucogenic hormone asprosin in ovarian cancer. Journal of Clinical Medicine, 11 (19). 5942. doi:10.3390/jcm11195942 ISSN 2077-0383.
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WRAP-Differential-regulation-genes-glucogenic-hormone-asprosin-ovarian-cancer-22.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (4Mb) | Preview |
Official URL: https://doi.org/10.3390/jcm11195942
Abstract
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. RNA sequencing, functional gene enrichment analysis, Western blotting and ImageStream. 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 ( < 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. 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.
Item Type: | Journal Article | |||||||||
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Subjects: | R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer) | |||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Medicine > Warwick Medical School | |||||||||
SWORD Depositor: | Library Publications Router | |||||||||
Library of Congress Subject Headings (LCSH): | Ovaries -- Cancer -- Genetic aspects, Ovaries -- Cancer, Ovaries -- Cancer -- Molecular aspects -- Research, Tumor markers -- Research, RNA -- Analysis | |||||||||
Journal or Publication Title: | Journal of Clinical Medicine | |||||||||
Publisher: | Royal College of Physicians | |||||||||
ISSN: | 2077-0383 | |||||||||
Official Date: | 8 October 2022 | |||||||||
Dates: |
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Volume: | 11 | |||||||||
Number: | 19 | |||||||||
Article Number: | 5942 | |||||||||
DOI: | 10.3390/jcm11195942 | |||||||||
Status: | Peer Reviewed | |||||||||
Publication Status: | Published | |||||||||
Access rights to Published version: | Open Access (Creative Commons) | |||||||||
Date of first compliant deposit: | 28 October 2022 | |||||||||
Date of first compliant Open Access: | 28 October 2022 | |||||||||
RIOXX Funder/Project Grant: |
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