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

被引:33
作者
Shen, Linhan [1 ]
Liu, Liu [1 ]
Ge, Liangyu [1 ]
Xie, Long [2 ]
Liu, Siyu [1 ]
Sang, Lei [3 ]
Zhan, Tiantian [1 ]
Li, Hongwei [1 ,4 ]
机构
[1] Nanjing Med Univ, Inst Stomatol, Affiliated Hosp Stomatol, Jiangsu Key Lab Oral Dis, Nanjing 210029, Jiangsu, Peoples R China
[2] Wuhan Univ, Hosp Stomatol, Dept Oral & Maxillofacial Surg, Wuhan 430079, Hubei, Peoples R China
[3] Suzhou Huaxia Stomatol Hosp, Dept Oral & Maxillofacial Surg, Suzhou 215002, Jiangsu, Peoples R China
[4] Nanjing Med Univ, Affiliated Hosp Stomatol, Dept Oral & Maxillofacial Surg, Jiangsu Key Lab Oral Dis, 136 Hanzhong Rd, Nanjing 210029, Jiangsu, Peoples R China
关键词
oral squamous cell carcinoma; miR-448; MPPED2; EXPRESSION; MICRORNAS; TUMOR; IDENTIFICATION; ASSOCIATION; METASTASIS; CAVITY; CARIES; GENES;
D O I
10.3892/etm.2016.3659
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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 in vitro. 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.
引用
收藏
页码:2747 / 2752
页数:6
相关论文
共 28 条
[1]   The functions of animal microRNAs [J].
Ambros, V .
NATURE, 2004, 431 (7006) :350-355
[2]   Human microRNA genes are frequently located at fragile sites and genomic regions involved in cancers [J].
Calin, GA ;
Sevignani, C ;
Dan Dumitru, C ;
Hyslop, T ;
Noch, E ;
Yendamuri, S ;
Shimizu, M ;
Rattan, S ;
Bullrich, F ;
Negrini, M ;
Croce, CM .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (09) :2999-3004
[3]   Cancer of the oral cavity: A comparison between institutions in a developing and a developed nation [J].
Carvalho, AL ;
Singh, B ;
Spiro, RH ;
Kowalski, LP ;
Shah, JP .
HEAD AND NECK-JOURNAL FOR THE SCIENCES AND SPECIALTIES OF THE HEAD AND NECK, 2004, 26 (01) :31-38
[4]   Abnormal expression of PER1 circadian-clock gene in oral squamous cell carcinoma [J].
Chen, Rui ;
Yang, Kai ;
Zhao, Ning-Bo ;
Zhao, Dan ;
Chen, Dan ;
Zhao, Chun-Rong ;
Tang, Hong .
ONCOTARGETS AND THERAPY, 2012, 5 :403-407
[5]   Increased LDH5 expression is associated with lymph node metastasis and outcome in oral squamous cell carcinoma [J].
Grimm, Martin ;
Alexander, Dorothea ;
Munz, Adelheid ;
Hoffmann, Juergen ;
Reinert, Siegmar .
CLINICAL & EXPERIMENTAL METASTASIS, 2013, 30 (04) :529-540
[6]   Identification of increased NBS1 expression as a prognostic marker of squamous cell carcinoma of the oral cavity [J].
Hsu, Dennis Shin-Shian ;
Chang, Shyue-Yih ;
Liu, Chung-Ji ;
Tzeng, Cheng-Hwai ;
Wu, Kou-Juey ;
Kao, Jung-Yie ;
Yang, Muh-Hwa .
CANCER SCIENCE, 2010, 101 (04) :1029-1037
[7]   miR-31 is upregulated in oral premalignant epithelium and contributes to the immortalization of normal oral keratinocytes [J].
Hung, Pei-Shih ;
Tu, Hsi-Feng ;
Kao, Shou-Yen ;
Yang, Cheng-Chieh ;
Liu, Chung-Ji ;
Huang, Ting-Yun ;
Chang, Kuo-Wei ;
Lin, Shu-Chun .
CARCINOGENESIS, 2014, 35 (05) :1162-1171
[8]   MicroRNAs in Cancer: Small Molecules With a Huge Impact [J].
Iorio, Marilena V. ;
Croce, Carlo M. .
JOURNAL OF CLINICAL ONCOLOGY, 2009, 27 (34) :5848-5856
[9]  
Jeong SH, 2013, KOREAN J NEUROTRAUMA, V9, P41, DOI 10.13004/kjnt.2013.9.2.41
[10]   microRNAs as tumor inhibitors, oncogenes, biomarkers for drug efficacy and outcome predictors in lung cancer [J].
Jiang, Yan-Wen ;
Chen, Liang-An .
MOLECULAR MEDICINE REPORTS, 2012, 5 (04) :890-894