miR-33a-5p in small extracellular vesicles as non-invasive biomarker for oxaliplatin sensitivity in human colorectal cancer cells

• Published in: Biochemistry and biophysics reports 2021-07, Vol.26, p.100996-100996, Article 100996
• Main Authors: Tanaka, Shota, Hosokawa, Mika, Miyamoto, Takumi, Nakagawa, Aiko, Haruna, Mika, Ueda, Kumiko, Iwakawa, Seigo, Ogawara, Ken-ichi
• Format: Article
• Language: English
• Subjects: Biomarker; Colorectal cancer; Extracellular microRNA; Liquid biopsy; Oxaliplatin; Small extracellular vesicles
• ISSN: 2405-5808; 2405-5808
• DOI: 10.1016/j.bbrep.2021.100996

microRNAs (miRNAs) contained in small extracellular vesicles (sEVs) are candidates for non-invasive biomarkers. Oxaliplatin (L-OHP) has been approved for advanced colorectal cancer (CRC) chemotherapy. However, the response to L-OHP differs among CRC patients. In addition, CRC cells often acquire the resistance to L-OHP. This study aimed at the prediction of L-OHP sensitivity by measuring extracellular miRNAs levels. Firstly, we compared intracellular miRNAs expressions in L-OHP-sensitive CRC cells (SW620 and HCT116 cells) with those in acquired and intrinsic L-OHP-resistant cells. In microarray and real-time RT-PCR analyses, the intracellular miR-33a-5p, miR-210–3p, and miR-224–5p expressions were lower in acquired and intrinsic L-OHP-resistant CRC cells than sensitive cells. Furthermore, in SW620 cells, L-OHP sensitivity was decreased by miR-33a-5p inhibitor. On the other hand, miR-210–3p or miR-224–5p inhibitor did not affect L-OHP sensitivity in SW620 cells. Secondly, the amount of miR-33a-5p, miR-210–3p, and miR-224–5p in sEVs was compared. The amount of miR-33a-5p and miR-210–3p in sEVs secreted from acquired and intrinsic L-OHP-resistant cells tended to be small. miR-224–5p was not detected in sEVs secreted from three types of CRC cells examined. To the best of our knowledge, this is the first study demonstrating that miR-33a-5p and/or miR-210–3p in sEVs would be candidates for biomarkers of L-OHP sensitivity. In particular, miR-33a-5p is a promising candidate because it would be directly involved in L-OHP sensitivity. [Display omitted] •miR-33a-5p was down-regulated in oxaliplatin-resistant colorectal cancer cells.•Reduction of intracellular miR-33a-5p expression caused oxaliplatin resistance.•miR-33a-5p amount in small extracellular vesicles from resistant cells was small.•miR-33a-5p is a candidate for non-invasive biomarker of oxaliplatin sensitivity.