Profiling of Exosomal Circular RNA in Folfox-Resistant Colon Cancer Cells

Abstract

Event Abstract Back to Event Profiling of exosomal circular RNA in Folfox-resistant colon cancer cells Kha Wai Hon1, Nadiah Abu1*, Nurul-Syakima Ab Mutalib1 and Rahman Jamal1 1 UKM Medical Molecular Biology Institute (UMBI), Malaysia Background Exosomes are extracellular nanovesicles released by almost all living cells including colorectal cancer cells (CRC) into biological fluids. Exosomes are natural carriers of proteins and nucleic acids that reflects parent cells. Exosomes have been investigated extensively as potential biomarkers and therapeutic targets for various diseases. However, the potential of exosomes as biomarkers to detect Folfox-resistant CRC has not been fully explored and validated. This research aimed to characterise exosomes derived from Folfox-resistant HCT116 CRC cell line as potential targets for further development of biomarkers among CRC patients with chemo-resistance. Methods Normal CRC cell line HCT116 (HCT116-C) was induced with 5 cycles of drug treatment to develop corresponding Folfox-resistant derivative clones (HCT116-R). HCT116-C and HCT116-R cell lines were compared for cell viability in 5-FU and oxaliplatin, wound healing assay, migration and invasion. Exosomes derived from both cell lines were characterised by transmission electron microscopy, particle size measurement, zeta potential analysis and Western Blot. Total RNA isolated from the exosomes of each cell line was subjected for circular RNA microarray. Selected circular RNAs were validated in clinical samples via RT-PCR. Results As compared to normal HCT116-C cell line, HCT116-R cell line had higher IC50 values with 2.5 to 6-fold change. Migration rate of HCT116-R cell line was 19 percent higher than HCT116-C cell line in wound healing assay. Exosomes from both cell lines were morphologically cup-shaped nanovesicles that range from 60 to 370nm in size with zeta potential between -29.1mV and -16.3mV. 105 circular RNAs were upregulated and 34 circular RNAs were downregulated in exosomes derived from HCT116-R against HCT116-C cells. Conclusion We developed a stable HCT116-Folfox resistant CRC cells, and the characteristics of exosomes derived from parental and resistant cell lines is in concordance with the literature. We have identified several circular RNAs in exosomes as potential biomarkers to predict Folfox-responsiveness. Acknowledgements This project was funded by the Dana Impak Perdana Grant (DIP-2016-013) awarded by Universiti Kebangsaan Malaysia. Keywords: Exosomes, colorectal cancer, molecular target, FOLFOX, biomarker Conference: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”, Putrajaya, Malaysia, 3 Dec - 5 Feb, 2019. Presentation Type: Poster Presentation Topic: Cancer Citation: Hon K, Abu N, Ab Mutalib N and Jamal R (2019). Profiling of exosomal circular RNA in Folfox-resistant colon cancer cells. Front. Pharmacol. Conference Abstract: International Conference on Drug Discovery and Translational Medicine 2018 (ICDDTM '18) “Seizing Opportunities and Addressing Challenges of Precision Medicine”. doi: 10.3389/conf.fphar.2018.63.00143 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 29 Nov 2018; Published Online: 17 Jan 2019. * Correspondence: Dr. Nadiah Abu, UKM Medical Molecular Biology Institute (UMBI), Kuala Lumpur, Malaysia, nadiah.abu@ppukm.ukm.edu.my Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Kha Wai Hon Nadiah Abu Nurul-Syakima Ab Mutalib Rahman Jamal Google Kha Wai Hon Nadiah Abu Nurul-Syakima Ab Mutalib Rahman Jamal Google Scholar Kha Wai Hon Nadiah Abu Nurul-Syakima Ab Mutalib Rahman Jamal PubMed Kha Wai Hon Nadiah Abu Nurul-Syakima Ab Mutalib Rahman Jamal Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.