MiR-320a acts as a prognostic factor and Inhibits metastasis of salivary adenoid cystic carcinoma by targeting ITGB3.
BACKGROUND
Salivary Adenoid cystic carcinoma (SACC) patients with local invasion and lung metastasis are often resistant to conventional therapy such as operation, chemotherapy and radiotherapy. To explore the underling mechanisms, we studied the roles of miRNA in regulating invasiveness of SACC cells.


METHODS
MicroRNA profiling was done in SACC cells with microarray. MiRNA mimics or antisense oligonucleotide was transfected and invasiveness of SACC cells was evaluated by adhesion assay and transwell assay. The target gene of miRNA was identified by luciferase reporter assay and "rescue" experiment. Tumor metastasis was evaluated by BALB/c-nu mice xenografts. MiRNA and its target gene expression were identified by in-situ hybridization and immunohistochemistry respectively, in 302 patients from affiliated hospitals of Sun Yat-sen University and in 148 patients from affiliated hospitals of Central South University, and correlated to the clinicopathological status of the patients.


RESULTS
MiR-320a was down-regulated in high lung metastatic ACCM and SACC-LM cells compared with the corresponding low metastatic ACC2 and SACC-83 cells, and inhibited adhesion, invasion and migration of SACC cells by targeting integrin beta 3 (ITGB3). In vivo, enforced miR-320a expression suppressed metastasis of SACC xenografts. In the two independent sets, miR-320a was downregulated in primary SACCs with metastasis compared to those without metastasis, and low expression of this miRNA predicts poor patient survival and rapid metastasis. Multivariate analysis showed that miR-320a expression was an independent indicator of lung metastasis.


CONCLUSIONS
MiR-320a inhibits metastasis in SACCs by targeting ITGB3 and may serve as a therapeutic target and prognostic marker in salivary cancers.
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. sunlj1186@163.com.|Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. sunlj1186@163.com.|Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. sunlj1186@163.com.
Lijuan
L
Sun
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. liuleopold@gmail.com.|Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. liuleopold@gmail.com.
Bodu
B
Liu
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. linzhaoyu163@163.com.|Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. linzhaoyu163@163.com.
Zhaoyu
Z
Lin
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. yyandan@126.com.|Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. yyandan@126.com.
Yandan
Y
Yao
Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. manple@163.com.
Yanyang
Y
Chen
Department of Pathology, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, China. li_yang_yang99@aliyun.com.
Yang
Y
Li
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. hulimsc@163.com.|Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. hulimsc@163.com.
Jianing
J
Chen
Guanghua School of Stomatology, Sun Yat-sen University, Guangzhou, 510055, China. gdyudongsheng@yahoo.com.cn.
Dongsheng
D
Yu
Xiangya School of Stomatology, Central South University, Changsha, 410078, China. tangzhangui@yahoo.com.cn.
Zhangui
Z
Tang
Xiangya School of Stomatology, Central South University, Changsha, 410078, China. victorwbs@163.com.
Bosheng
B
Wang
Guangdong Provincial Stomatological Hospital, Guangzhou, 510280, China. sunrisez@tom.com.
Shuguang
S
Zeng
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. fansong8888@163.com.|Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. fansong8888@163.com.
Song
S
Fan
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. sumswangyy@163.com.|Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. sumswangyy@163.com.
Youyuan
Y
Wang
Xaverian Brothers High School, Westwood, MA, 02090, USA. lizhihu1996@gmail.com.
Yilin
Y
Li
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. songerwei02@aliyun.com.|Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. songerwei02@aliyun.com.|Sun Yatsen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. songerwei02@aliyun.com.
Erwei
E
Song
Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, China. lijinsong1967@163.com.|Department of Oral & Maxillofacial Surgery, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. lijinsong1967@163.com.|Sun Yatsen Memorial Hospital, Sun Yat-sen University, Guangzhou, 510120, China. lijinsong1967@163.com.
Jinsong
J
Li
D000818:Animals; D001483:Base Sequence; D003528:Carcinoma, Adenoid Cystic / Q000235:genetics* / Q000473:pathology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005260:Female; D006801:Humans; D039661:Integrin beta3 / Q000235:genetics / Q000378:metabolism*; D008175:Lung Neoplasms / Q000556:secondary*; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009361:Neoplasm Invasiveness; D011379:Prognosis; D012468:Salivary Gland Neoplasms / Q000235:genetics* / Q000473:pathology*; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
C061248:ITGB3 protein, human; D039661:Integrin beta3; C572916:MIRN320 microRNA, human; D035683:MicroRNAs