EBV-miR-BART10-3p facilitates epithelial-mesenchymal transition and promotes metastasis of nasopharyngeal carcinoma by targeting BTRC.
Epstein-Barr virus (EBV) infection is closely associated with tumorigenesis and development of nasopharyngeal carcinoma (NPC), but the underlying molecular mechanisms remain poorly understood. It has been recently reported that EBV encodes 44 mature miRNAs, some of which were found to promote tumor development by targeting virus-infected host genes or self-viral genes. However, few targets of EBV encoded-miRNAs that are related to NPC development have been identified to date. In this study, we revealed that in NPC cells, EBV-miR-BART10-3p directly targets BTRC gene that encodes βTrCP (beta-transducin repeat containing E3 ubiquitin protein ligase). We found that EBV-miR-BART10-3p expression in clinical samples from a cohort of 106 NPC patients negatively correlated with BTRC expression levels. Over-expression of EBV-miR-BART10-3p and down-regulation of BTRC were associated with poor prognosis in NPC patients. EBV-miR-BART10-3p promoted the invasion and migration cabilities of NPC cells through the targeting of BTRC and regulation of the expression of the downstream substrates β-catenin and Snail. As a result, EBV-miR-BART10-3p facilitated epithelial-mesenchymal transition of NPC. Our study presents an unreported mechanism underlying EBV infection in NPC carcinogenesis, and provides a potential novel biomarker for NPC diagnosis, treatment and prognosis.
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Qijia
Q
Yan
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhaoyang
Z
Zeng
The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Zhaojian
Z
Gong
The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Wenling
W
Zhang
Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiayu
X
Li
The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Baoyu
B
He
The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Yali
Y
Song
The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.
Qiao
Q
Li
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Yong
Y
Zeng
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Qianjin
Q
Liao
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Pan
P
Chen
The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Lei
L
Shi
The Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Songqing
S
Fan
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Bo
B
Xiang
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Jian
J
Ma
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Ming
M
Zhou
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Xiaoling
X
Li
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|Department of Laboratory Medicine and Pathology and Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota, United States of America.
Jianbo
J
Yang
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Wei
W
Xiong
Hunan Key Laboratory of Translational Radiation Oncology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha, Hunan, China.|The Key Laboratory of Carcinogenesis of The Chinese Ministry of Health and The Key Laboratory of Carcinogenesis and Cancer Invasion of The Chinese Ministry of Education, Cancer Research Institute, Central South University, Changsha, Hunan, China.|Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Disease Genome Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
Guiyuan
G
Li
D002277:Carcinoma; D045744:Cell Line, Tumor; D002465:Cell Movement; D018572:Disease-Free Survival; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D053208:Kaplan-Meier Estimate; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D000077274:Nasopharyngeal Carcinoma; D009303:Nasopharyngeal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000401:mortality / Q000473:pathology / Q000628:therapy / Q000821:virology; D009361:Neoplasm Invasiveness; D012367:RNA, Viral / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D000071250:Snail Family Transcription Factors; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D016896:Treatment Outcome; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics* / Q000378:metabolism
C471644:BTRC protein, human; C495270:CTNNB1 protein, human; C000611108:EBV-BART10-3p microRNA; D035683:MicroRNAs; D012367:RNA, Viral; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D051176:beta Catenin; D044844:beta-Transducin Repeat-Containing Proteins
BTRC; EBV-miR-BART10-3p; Epstein-Barr virus (EBV); epithelial-mesenchymal transition (EMT); nasopharyngeal carcinoma (NPC)