Wang Xijun, Guo Hongmei, Yao Banjamin, Helms Julia
Department of Prosthodontics, School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China.
Department of Periodontology, School of Stomatology, Shandong University, Jinan, Shandong 250012, P.R. China.
Oncol Rep. 2017 May;37(5):2720-2726. doi: 10.3892/or.2017.5532. Epub 2017 Mar 27.
Oral tongue squamous cell carcinoma (TSCC) is one of the most lethal cancers within the oral cavity and its prognosis remains dismal due to the paucity of effective therapeutic targets. The formation of cancer-initiating cells (CICs) and epithelial-mesenchymal transition (EMT) are pivotal events involved in the dismal prognosis. They have been shown to be related to the resistance to cisplatin treatment. In the present study, we showed that TRIM14 induced formation of cancer-initiating cells and EMT in TSCC SCC25 cells. Its overexpression promoted cisplatin resistance in the SCC25 cells. We found that overexpression of miR-15b suppressed TRIM14 and inhibited CIC phenotypes in the SCC25 cells. Moreover, overexpression of miR-15b promoted mesenchymal-epithelial transition (MET) in the SCC25 cells and sensitized cisplatin-resistant SCC25 (SCC25-res) cells to cisplatin. Thus, we conclude that miR-15b inhibited cancer stem cell phenotypes and its restoration reversed the chemoresistance of cisplatin by targeting TRIM14 in TSCC. Elucidating the molecular mechanism of EMT and cancer stem cells in TSCC may further aid in the understanding of the pathogenesis and progression of the disease, and offer novel targets for the discovery of new drugs.
口腔舌鳞状细胞癌（TSCC）是口腔中最致命的癌症之一，由于缺乏有效的治疗靶点，其预后仍然很差。癌症起始细胞（CIC）的形成和上皮-间质转化（EMT）是导致预后不良的关键事件。它们已被证明与顺铂治疗的耐药性有关。在本研究中，我们发现TRIM14在TSCC SCC25细胞中诱导癌症起始细胞的形成和EMT。其过表达促进了SCC25细胞对顺铂的耐药性。我们发现miR-15b的过表达抑制了TRIM14，并抑制了SCC25细胞中的CIC表型。此外，miR-15b的过表达促进了SCC25细胞中的间质-上皮转化（MET），并使顺铂耐药的SCC25（SCC25-res）细胞对顺铂敏感。因此，我们得出结论，miR-15b通过靶向TSCC中的TRIM14抑制癌症干细胞表型，其恢复逆转了顺铂的化疗耐药性。阐明TSCC中EMT和癌症干细胞的分子机制可能有助于进一步理解该疾病的发病机制和进展，并为发现新药提供新的靶点。
