Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Jilin University, Changchun, Jilin 130021, P.R. China.
Department of Thoracic Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China.
Oncol Rep. 2018 Mar;39(3):1173-1180. doi: 10.3892/or.2017.6157. Epub 2017 Dec 15.
MicroRNA‑152 (miR‑152) has been reported to be involved in tumor development and progression in multiple cancers. However, the expression level, biological function and regulatory mechanisms of miR‑152 in oral squamous cell carcinoma cells (OSCC) remain unclear. The aims of this study were therefore to investigate the role of miR‑152 in OSCC and the relevant mechanism. It was found that miR‑152 was downregulated in OSCC cell lines and tissues, and that decreased miR‑152 was closely associated with lymph node metastasis, and patient survival rate. In vitro restoration of miR‑152 significantly repressed cell proliferation, colony formation, migration and invasion of OSCC cells. Notably, cellular-mesenchymal to epithelial transition factor (c‑MET) and its downstream signaling pathway (PI3K/AKT) was downregulated in OSCC cells by miR‑152 through direct interactions with its 3' untranslated region. Restoring c‑MET expression attenuated miR‑152-induced inhibitory effects in OSCC cells. In vivo study confirmed that restoration of miR‑152 suppressed tumor growth in xenograft nude mice by repressing c‑MET. In summary, the present study highlight miR‑152 as a tumor suppressor in OSCC through direct targeting c‑MET, rendering miR‑152 a promising therapeutic target for oral squamous cell carcinoma.
微小 RNA-152 (miR-152) 已被报道参与多种癌症的肿瘤发生和进展。然而，miR-152 在口腔鳞状细胞癌 (OSCC) 细胞中的表达水平、生物学功能和调控机制仍不清楚。因此，本研究旨在探讨 miR-152 在 OSCC 中的作用及其相关机制。研究发现，miR-152 在 OSCC 细胞系和组织中下调，且 miR-152 的降低与淋巴结转移和患者生存率密切相关。体外恢复 miR-152 显著抑制 OSCC 细胞的增殖、集落形成、迁移和侵袭。值得注意的是，miR-152 通过与其 3'UTR 的直接相互作用下调了 OSCC 细胞中的上皮间质转化因子 (c-MET) 及其下游信号通路 (PI3K/AKT)。恢复 c-MET 表达可减弱 miR-152 对 OSCC 细胞的抑制作用。体内研究证实，恢复 miR-152 通过抑制 c-MET 抑制异种移植裸鼠肿瘤生长。综上所述，本研究通过直接靶向 c-MET 强调了 miR-152 在 OSCC 中的肿瘤抑制作用，使 miR-152 成为口腔鳞状细胞癌有前途的治疗靶点。
