Extracellular Vesicle-derived circular RNAs confers chemoresistance in Colorectal cancer

Kha Wai Hon, Nurul Syakima Ab-Mutalib, Nik Muhd Aslan Abdullah, Rahman Jamal, Nadiah Abu

Research output: Contribution to journalArticle

Abstract

Chemo-resistance is associated with poor prognosis in colorectal cancer (CRC), with the absence of early biomarker. Exosomes are microvesicles released by body cells for intercellular communication. Circular RNAs (circRNAs) are non-coding RNAs with covalently closed loops and enriched in exosomes. Crosstalk between circRNAs in exosomes and chemo-resistance in CRC remains unknown. This research aims to identify exosomal circRNAs associated with FOLFOX-resistance in CRC. FOLFOX-resistant HCT116 CRC cells (HCT116-R) were generated from parental HCT116 cells (HCT116-P) using periodic drug induction. Exosomes were characterized using transmission electron microscopy (TEM), Zetasizer and Western blot. Our exosomes were translucent cup-shaped structures under TEM with differential expression of TSG101, CD9, and CD63. We performed circRNAs microarray using exosomal RNAs from HCT116-R and HCT116-P cells. We validated our microarray data using serum samples. We performed drug sensitivity assay and cell cycle analysis to characterize selected circRNA after siRNA-knockdown. Using fold change >2 and p < 0.05, we identified 105 significantly upregulated and 34 downregulated circRNAs in HCT116-R exosomes. Knockdown of circ_0000338 improved the chemo-resistance of CRC cells. We have proposed that circ_0000338 may have dual regulatory roles in chemo-resistant CRC. Exosomal circ_0000338 could be a potential biomarker for further validation in CRC.

Original languageEnglish
Article number16497
JournalScientific reports
Volume9
Issue number1
DOIs
Publication statusPublished - 1 Dec 2019

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Exosomes
Colorectal Neoplasms
HCT116 Cells
Transmission Electron Microscopy
Exosome Multienzyme Ribonuclease Complex
Biomarkers
Untranslated RNA
circular RNA
Extracellular Vesicles
Cell Communication
Pharmaceutical Preparations
Small Interfering RNA
Cell Cycle
Down-Regulation
Western Blotting
RNA
Serum
Research

ASJC Scopus subject areas

  • General

Cite this

Extracellular Vesicle-derived circular RNAs confers chemoresistance in Colorectal cancer. / Hon, Kha Wai; Ab-Mutalib, Nurul Syakima; Abdullah, Nik Muhd Aslan; Jamal, Rahman; Abu, Nadiah.

In: Scientific reports, Vol. 9, No. 1, 16497, 01.12.2019.

Research output: Contribution to journalArticle

Hon, Kha Wai ; Ab-Mutalib, Nurul Syakima ; Abdullah, Nik Muhd Aslan ; Jamal, Rahman ; Abu, Nadiah. / Extracellular Vesicle-derived circular RNAs confers chemoresistance in Colorectal cancer. In: Scientific reports. 2019 ; Vol. 9, No. 1.
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