Department of Oral and Maxillofacial Functional Rehabilitation, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan.
Anticancer Res. 2020 Nov;40(11):6101-6113. doi: 10.21873/anticanres.14631.
BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is a common malignancy with poor prognosis. Therefore, novel therapeutic options are needed to improve prognosis of OSCC. Recently, microRNAs (miRs) have received increasing attention as a potential therapeutic tool for carcinomas. However, no definitive miR-based drugs for patients with OSCC have been reported to date. The aim of this study was to identify new miRs potentially involved in cellular processes associated with OSCC malignancy, which could lead to novel therapeutic strategies.
We identified miRs that are modulated in OSCC and possibly regulate OSCC malignancy, using miR microarray on OSCC cell lines.
miR-935 and miR-509-3p were down-regulated in OSCC cell lines and patient tissues. When miR-935 was overexpressed in HSC-3-M3 cells, proliferation, migration, and invasion of the cell line was suppressed, whereas apoptosis was increased. Moreover, we showed that the gene inositol polyphosphate-4-phosphatase type I A (INPP4A) is a potential target whose expression is positively regulated by miR-935.
miR-935 may function as a tumor suppressor by inhibiting OSCC malignancy via INPP4A induction. Therefore, miR-935 can be a new therapeutic candidate for OSCC treatment.
背景/目的：口腔鳞状细胞癌（OSCC）是一种预后较差的常见恶性肿瘤。因此，需要新的治疗方法来改善 OSCC 的预后。最近，microRNAs（miRs）作为治疗癌症的潜在工具受到了越来越多的关注。然而，迄今为止，尚无针对 OSCC 患者的基于 miR 的明确药物。本研究旨在鉴定与 OSCC 恶性相关的细胞过程中可能涉及的新的 miR，从而为新的治疗策略提供依据。
我们使用 OSCC 细胞系上的 miR 微阵列，鉴定了在 OSCC 细胞系中调节且可能调节 OSCC 恶性的 miR。
miR-935 和 miR-509-3p 在 OSCC 细胞系和患者组织中下调。当 miR-935 在 HSC-3-M3 细胞中过表达时，细胞系的增殖、迁移和侵袭受到抑制，而凋亡增加。此外，我们表明肌醇多磷酸-4-磷酸酶 I A（INPP4A）是一个潜在的靶基因，其表达受 miR-935 正向调节。
miR-935 可通过诱导 INPP4A 抑制 OSCC 恶性作为肿瘤抑制因子发挥作用。因此，miR-935 可以成为治疗 OSCC 的新的治疗候选物。
