Down-regulation of miRNA-204 by LMP-1 enhances CDC42 activity and facilitates invasion of EBV-associated nasopharyngeal carcinoma cells

Lei Ma; Xubin Deng; Minhua Wu; Gong Zhang; Jianqing Huang

doi:10.1016/j.febslet.2014.02.039

Down-regulation of miRNA-204 by LMP-1 enhances CDC42 activity and facilitates invasion of EBV-associated nasopharyngeal carcinoma cells

FEBS Lett. 2014 May 2;588(9):1562-70. doi: 10.1016/j.febslet.2014.02.039. Epub 2014 Mar 5.

Authors

Lei Ma¹, Xubin Deng¹, Minhua Wu², Gong Zhang³, Jianqing Huang⁴

Affiliations

¹ Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University (CCGMU), Guangzhou, People's Republic of China.
² Department of Histology and Embryology, Guangdong Medical College, Zhanjiang, People's Republic of China.
³ Department of Radiotherapy, People's Hospital of Shanxi Province, Taiyuan, People's Republic of China.
⁴ Affiliated Cancer Hospital of Guangzhou Medical University, Cancer Center of Guangzhou Medical University (CCGMU), Guangzhou, People's Republic of China. Electronic address: JianqingHuang_01@126.com.

PMID: 24613926
DOI: 10.1016/j.febslet.2014.02.039

Abstract

Nasopharayngeal carcinoma (NPC) is an Epstein-Barr virus (EBV)-associated malignancy. It is known that microRNAs are implicated in the progression of NPC. However, the role of miR-204 in NPC is poorly understood. In this study, we found that miR-204 was down-regulated in NPC cells and tissues. Low-level expression of miR-204 was significantly associated with a more aggressive and poor prognostic phenotype of NPC. We further found that EBV-encoded latent membrane protein 1 (LMP-1) suppressed miR-204 expression by activating Stat-3. Cdc42 was identified as a direct target of miR-204. Mir-204 inhibited EBV positive C666-1 cell invasion and metastasis partly through targeting cdc42.

Keywords: Cdc42; Epstein–Barr virus; Latent membrane protein 1; Nasopharyngeal carcinoma; Stat-3; miR-204.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Base Sequence
Binding Sites
Carcinoma
Cell Line, Tumor
Disease Progression
Down-Regulation
Epstein-Barr Virus Infections / metabolism*
Epstein-Barr Virus Infections / mortality
Epstein-Barr Virus Infections / pathology
Female
Gene Expression Regulation, Neoplastic
Herpesvirus 4, Human*
Humans
Kaplan-Meier Estimate
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / genetics*
MicroRNAs / metabolism
Middle Aged
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms / metabolism*
Nasopharyngeal Neoplasms / mortality
Nasopharyngeal Neoplasms / pathology
Nasopharyngeal Neoplasms / virology
Neoplasm Invasiveness
Neoplasm Transplantation
Prognosis
RNA Interference
STAT3 Transcription Factor / metabolism
Signal Transduction
Tumor Burden
Viral Matrix Proteins / physiology*
cdc42 GTP-Binding Protein / metabolism*

Substances

EBV-associated membrane antigen, Epstein-Barr virus
MIRN204 microRNA, human
MicroRNAs
STAT3 Transcription Factor
STAT3 protein, human
Viral Matrix Proteins
cdc42 GTP-Binding Protein