Ando Toshiaki, Kasamatsu Atsushi, Kawasaki Kohei, Hiroshima Kazuya, Fukushima Reo, Iyoda Manabu, Nakashima Dai, Endo-Sakamoto Yosuke, Uzawa Katsuhiro
Department of Oral Science, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Department of Dentistry and Oral-Maxillofacial Surgery, Chiba University Hospital, Chiba 260-8677, Japan.
Cancers (Basel). 2021 Nov 15;13(22):5708. doi: 10.3390/cancers13225708.
Circular RNAs (circRNAs), which form as covalently closed loop structures, have several biological functions such as regulation of cellular behavior by adsorbing microRNAs. However, there is limited information of circRNAs in oral squamous cell carcinoma (OSCC). Here, we aimed to elucidate the roles of aberrantly expressed circRNAs in OSCC. CircRNA microarray showed that circRNA-102450 was down-regulated in OSCC cells. Clinical validation of circRNA-102450 was performed using highly sensitive droplet digital PCR in preoperative liquid biopsy samples from 30 OSCC patients. Interestingly, none of 16 studied patients with high circRNA-102450 had regional lymph node metastasis (RLNM), whereas 4 of 14 studied patients (28.5%) with low expression had pathologically proven RLNM. Overexpressed circRNA-102450 significantly inhibited the tumor metastatic properties of cell proliferation, migration, and invasion. Furthermore, circRNA-102450 directly bound to, and consequently down-regulated, miR-1178 in OSCC cells. Taken together, circRNA-102450 has a tumor suppressive effect via the circRNA-102450/miR-1178 axis and may be a novel potential marker of RLNM in OSCC patients.
环状RNA(circRNAs)以共价闭合环结构形式存在,具有多种生物学功能,如通过吸附微小RNA来调节细胞行为。然而,关于口腔鳞状细胞癌(OSCC)中环状RNA的信息有限。在此,我们旨在阐明异常表达的环状RNA在OSCC中的作用。环状RNA微阵列显示,circRNA - 102450在OSCC细胞中表达下调。使用高灵敏度液滴数字PCR对30例OSCC患者术前液体活检样本中的circRNA - 102450进行临床验证。有趣的是,在16例circRNA - 102450高表达的研究患者中,无一例发生区域淋巴结转移(RLNM),而在14例低表达的研究患者中有4例(28.5%)经病理证实发生了RLNM。过表达的circRNA - 102450显著抑制细胞增殖、迁移和侵袭的肿瘤转移特性。此外,circRNA - 102450在OSCC细胞中直接与miR - 1178结合,从而下调miR - 1178。综上所述,circRNA - 102450通过circRNA - 102450/miR - 1178轴发挥肿瘤抑制作用,可能是OSCC患者RLNM的一种新型潜在标志物。