Tanaka Shota, Hosokawa Mika, Miyamoto Takumi, Nakagawa Aiko, Haruna Mika, Ueda Kumiko, Iwakawa Seigo, Ogawara Ken-Ichi
Biochem Biophys Rep. 2021 Apr 7;26:100996. doi: 10.1016/j.bbrep.2021.100996. eCollection 2021 Jul.
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.
小细胞外囊泡（sEVs）中含有的微小RNA（miRNAs）是非侵入性生物标志物的候选者。奥沙利铂（L-OHP）已被批准用于晚期结直肠癌（CRC）的化疗。然而，CRC患者对L-OHP的反应各不相同。此外，CRC细胞常常会对L-OHP产生耐药性。本研究旨在通过测量细胞外miRNAs水平来预测对L-OHP的敏感性。首先，我们比较了L-OHP敏感的CRC细胞（SW620和HCT116细胞）与获得性和固有性L-OHP耐药细胞中的细胞内miRNAs表达。在微阵列和实时RT-PCR分析中，获得性和固有性L-OHP耐药的CRC细胞中的细胞内miR-33a-5p、miR-210-3p和miR-224-5p表达低于敏感细胞。此外，在SW620细胞中，miR-33a-5p抑制剂降低了L-OHP敏感性。另一方面，miR-210-3p或miR-224-5p抑制剂对SW620细胞中的L-OHP敏感性没有影响。其次，比较了sEVs中miR-33a-5p、miR-210-3p和miR-224-5p的含量。获得性和固有性L-OHP耐药细胞分泌的sEVs中miR-33a-5p和miR-210-3p的含量往往较少。在所检测的三种CRC细胞分泌的sEVs中未检测到miR-224-5p。据我们所知，这是第一项证明sEVs中的miR-33a-5p和/或miR-210-3p可能是L-OHP敏感性生物标志物候选者的研究。特别是，miR-33a-5p是一个有前景的候选者，因为它可能直接参与L-OHP敏感性。
