Xu Ran, Zeng Guang, Gao Jing, Ren Yue, Zhang Zhe, Zhang Qingna, Zhao Jinxiu, Tao Hong, Li Daxu
Department of Stomatology, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Plastic and Burn Surgery, Tangdu Hospital, The Fourth Military Medical University, Xi'an, Shaanxi 710038, P.R. China.
Oncol Rep. 2015 Oct;34(4):2171-8. doi: 10.3892/or.2015.4144. Epub 2015 Jul 23.
Aberrant microRNA expression has been suggested to be an important event in the pathologies of various types of cancer. MicroRNA-138 (miR-138) has been reported to be frequently downregulated in various types of human cancer, including oral squamous cell carcinoma (OSCC). However, the precise molecular mechanism of miR-138 underlying OSCC remains largely unknown. The aim of the present study was to investigate the expression of miR-138 in OSCC tumor tissues and several OSCC cell lines and validated its interaction with the 3'-untranslated region (3'-UTR) of Yes-associated protein 1 (YAP1). The results showed that, miR-138 was significantly downregulated in OSCC tumor tissues and cell lines. Overexpression of miR-138 inhibited cell proliferation of OSCC cells whereas the downregulation of miR-138 promoted cell proliferation. A direct interaction between miR-138 and 3'-UTR of YAP1 was validated by dual-luciferase reporter assay. Moreover, overexpression of miR-138 in OSCC cells significantly decreased the expression of YAP1 and downregulation of miR-138 inhibited the expression of YAP1. Specifically, the inhibitory effect of miR-138 on the proliferation of OSCC cells was eliminated by transfection with YAP1 overexpression vectors that did not harbor any specific miR-138 binding specific sequences in 3'-UTR. In addition, the miR-138‑overexpressing OSCC cells exhibited a low growth rate in the xenograft tumor assay with a decreased expression of YAP1 in tumor tissues. The results suggest that miR-138 is a tumor suppressor miRNA in OSCC through targeting YAP1, which serves as a promising therapeutic target for the treatment of OSCC.
异常的微小RNA表达被认为是各类癌症病理过程中的一个重要事件。据报道，微小RNA - 138（miR - 138）在包括口腔鳞状细胞癌（OSCC）在内的各类人类癌症中经常下调。然而，miR - 138在OSCC中的确切分子机制仍 largely未知。本研究的目的是调查miR - 138在OSCC肿瘤组织和几种OSCC细胞系中的表达，并验证其与Yes相关蛋白1（YAP1）的3'非翻译区（3'-UTR）的相互作用。结果显示，miR - 138在OSCC肿瘤组织和细胞系中显著下调。miR - 138的过表达抑制了OSCC细胞的增殖，而miR - 138的下调则促进了细胞增殖。通过双荧光素酶报告基因检测验证了miR - 138与YAP1的3'-UTR之间的直接相互作用。此外，miR - 138在OSCC细胞中的过表达显著降低了YAP1的表达，而miR - 138的下调则抑制了YAP1的表达。具体而言，通过转染在3'-UTR中不包含任何特定miR - 138结合特异性序列的YAP1过表达载体，消除了miR - 138对OSCC细胞增殖的抑制作用。此外，在异种移植肿瘤试验中，过表达miR - 138的OSCC细胞生长速率较低，肿瘤组织中YAP1的表达降低。结果表明，miR - 138通过靶向YAP1是OSCC中的一种肿瘤抑制性微小RNA，这为OSCC的治疗提供了一个有前景的治疗靶点。
