Shandong Provincial Key Laboratory of Oral Tissue Regeneration, School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Stomatology, Zaozhuang Municipal Hospital, Zaozhuang, Shandong 277100, P.R. China.
Mol Med Rep. 2017 Nov;16(5):7245-7252. doi: 10.3892/mmr.2017.7531. Epub 2017 Sep 20.
Tongue squamous cell carcinoma (TSCC) is the most frequent type of oral carcinoma, and is characterized by high metastatic and growth capabilities. Previous studies have demonstrated that aberrantly expressed cancer‑associated microRNAs (miRs) may be associated with tumorigenesis and tumor development in various types of cancer, including TSCC. miR‑509 has been identified as a critical regulator in tumorigenesis and tumor development, via its tumor‑suppressing actions in several types of human cancer. In the present study, miR‑509 expression in TSCC tissues and cell lines was determined by reverse transcription‑quantitative polymerase chain reaction. The effects of miR‑509 on TSCC cell proliferation and invasion were evaluated via MTT and invasion assays, respectively. In addition, the direct target of miR‑509 in TSCC was investigated. The present study demonstrated that miR‑509 expression was downregulated in TSCC tissue samples and cell lines, whereas its ectopic expression suppressed TSCC cell proliferation and invasion in vitro. In addition, epidermal growth factor receptor (EGFR) was identified as a direct target gene of miR‑509 in TSCC cells. EGFR downregulation was demonstrated to suppress the proliferation and invasion of TSCC cells, similar to miR‑509 overexpression. Furthermore, EGFR was significantly upregulated in TSCC tissues, and the levels of miR‑509 were revealed to be negatively correlated with EGFR expression in TSCC tissues. Following transfection with miR‑509 mimics, signaling pathways downstream of EGFR appeared to be suppressed, as phosphorylated (p)‑extracellular signal‑regulated kinase and p‑Akt were downregulated in TSCC cells. In conclusion, the results of the present study suggested that miR‑509 may inhibit the proliferation and invasion of TSCC cells via directly targeting EGFR, thus suggesting that the miR‑509/EGFR axis may have potential as a novel therapeutic target for the development of a treatment for patients with TSCC.
舌鳞状细胞癌 (TSCC) 是最常见的口腔癌类型,其特征为高转移性和生长能力。先前的研究表明,异常表达的癌症相关 microRNAs (miRs) 可能与多种癌症(包括 TSCC)的肿瘤发生和肿瘤发展有关。miR-509 已被确定为一种关键的肿瘤发生和肿瘤发展调节剂,通过其在几种人类癌症中的肿瘤抑制作用。在本研究中,通过逆转录-定量聚合酶链反应测定 TSCC 组织和细胞系中的 miR-509 表达。通过 MTT 和侵袭试验分别评估 miR-509 对 TSCC 细胞增殖和侵袭的影响。此外,还研究了 miR-509 在 TSCC 中的直接靶标。本研究表明,miR-509 在 TSCC 组织样本和细胞系中表达下调,而其异位表达可抑制 TSCC 细胞的体外增殖和侵袭。此外,表皮生长因子受体 (EGFR) 被鉴定为 TSCC 细胞中 miR-509 的直接靶基因。EGFR 下调被证明可抑制 TSCC 细胞的增殖和侵袭,与 miR-509 过表达相似。此外,EGFR 在 TSCC 组织中明显上调,miR-509 的水平与 TSCC 组织中 EGFR 的表达呈负相关。转染 miR-509 模拟物后,EGFR 下游信号通路似乎被抑制,因为 TSCC 细胞中的磷酸化 (p)-细胞外信号调节激酶和 p-Akt 下调。总之,本研究结果表明,miR-509 可能通过直接靶向 EGFR 抑制 TSCC 细胞的增殖和侵袭,提示 miR-509/EGFR 轴可能作为开发治疗 TSCC 患者的新治疗靶点具有潜力。