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微小RNA-448通过下调MPPED2促进口腔鳞状细胞癌的癌细胞增殖并抑制细胞凋亡。

miR-448 downregulates MPPED2 to promote cancer proliferation and inhibit apoptosis in oral squamous cell carcinoma.

作者信息

Shen Linhan, Liu Liu, Ge Liangyu, Xie Long, Liu Siyu, Sang Lei, Zhan Tiantian, Li Hongwei

机构信息

Jiangsu Key Laboratory of Oral Diseases, Institute of Stomatology, Affiliated Hospital of Stomatology, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Department of Oral and Maxillofacial Surgery, Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, P.R. China.

出版信息

Exp Ther Med. 2016 Oct;12(4):2747-2752. doi: 10.3892/etm.2016.3659. Epub 2016 Sep 5.

Abstract

The incidence of oral squamous cell carcinoma (OSCC) is continuously increasing while its survival rate has not notably improved. There is a pressing need for improved understanding of the genetic regulation of OSCC tumorigenesis and progression. In this study, the function of miR-448 in the regulation of OSCC growth and its putative target were thoroughly analyzed . The expression of miR-448 was detected in human OSCC specimens and OSCC cell lines (Cal-27 and Scc-9) by reverse transcription-quantitative polymerase chain reaction. The function of miR-448 was investigated in Cal-27 cells transfected with miR-448 inhibitor, and its putative target determined using a luciferase reporter assay. MTT and wound healing assays and flow cytometry were used to evaluate the effects of miR-448 on OSCC proliferation, metastasis and apoptosis. The level of miR-448 was significantly elevated in human OSCC tissues and the Cal-27 cell line. Suppression of miR-448 expression attenuated cell proliferation and migration, and induced apoptosis of Cal-27 cells. Furthermore, miR-448 bound with the 3'-untranslated region of metallophosphoesterase domain containing 2 (MPPED2) mRNA, thereby reducing the MPPED2 protein level. Thus, it appears that miR-448 acts as a tumor inducer, causing OSCC growth by inhibiting the expression of its target MPPED2. These results demonstrate that miR-448 plays a critical role in OSCC tumorigenesis, and is a potential therapeutic target.

摘要

口腔鳞状细胞癌(OSCC)的发病率持续上升,但其生存率并未显著提高。迫切需要更好地了解OSCC肿瘤发生和进展的基因调控。在本研究中,对miR-448在OSCC生长调控中的功能及其潜在靶点进行了深入分析。通过逆转录-定量聚合酶链反应检测人OSCC标本和OSCC细胞系(Cal-27和Scc-9)中miR-448的表达。在转染了miR-448抑制剂的Cal-27细胞中研究miR-448的功能,并使用荧光素酶报告基因测定法确定其潜在靶点。采用MTT、伤口愈合试验和流式细胞术评估miR-448对OSCC增殖、转移和凋亡的影响。miR-448在人OSCC组织和Cal-27细胞系中的水平显著升高。抑制miR-448表达可减弱细胞增殖和迁移,并诱导Cal-27细胞凋亡。此外,miR-448与含金属磷酸酯酶结构域2(MPPED2)mRNA的3'-非翻译区结合,从而降低MPPED2蛋白水平。因此,miR-448似乎作为一种肿瘤诱导因子,通过抑制其靶点MPPED2的表达导致OSCC生长。这些结果表明,miR-448在OSCC肿瘤发生中起关键作用,是一个潜在的治疗靶点。

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