miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma

Min Deng; Hailin Tang; Yanhong Zhou; Ming Zhou; Wei Xiong; Ying Zheng; Qiurong Ye; Xi Zeng; Qianjin Liao; Xiaofang Guo; Xiaoling Li; Jian Ma; Guiyuan Li

doi:10.1242/jcs.085050

miR-216b suppresses tumor growth and invasion by targeting KRAS in nasopharyngeal carcinoma

J Cell Sci. 2011 Sep 1;124(Pt 17):2997-3005. doi: 10.1242/jcs.085050.

Authors

Min Deng¹, Hailin Tang, Yanhong Zhou, Ming Zhou, Wei Xiong, Ying Zheng, Qiurong Ye, Xi Zeng, Qianjin Liao, Xiaofang Guo, Xiaoling Li, Jian Ma, Guiyuan Li

Affiliation

¹ Cancer Research Institute, Central South University, 110 Xiang-Ya Road, Changsha 410078, Hunan, People's Republic of China.

PMID: 21878506
DOI: 10.1242/jcs.085050

Abstract

MicroRNAs (miRNAs) are small noncoding RNAs that are involved in various diseases, including cancer. In the present study, we found that miR-216b was downregulated in nasopharyngeal carcinoma (NPC) cell lines and specimens. Decreased expression of miR-216b was directly related to advanced clinical stage and lymph node metastasis. miR-216b levels correlated inversely with levels of KRAS protein during nasopharyngeal tumorigenesis. Furthermore, we demonstrated that miR-216b can bind to the 3' untranslated region (UTR) of KRAS and inhibit expression of the KRAS protein. Both in vitro and in vivo assays revealed that miR-216b attenuated NPC cell proliferation, invasion and tumor growth in nude mice. miR-216b exerts its tumor suppressor function through inhibition of the KRAS-related AKT and ERK pathways. Our findings provide, for the first time, significant clues regarding the role of miR-216b as a tumor suppressor by targeting KRAS in NPC.

Publication types

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

MeSH terms

3' Untranslated Regions
Animals
Carcinoma
Cell Growth Processes / genetics
Cell Line, Tumor
Down-Regulation
Extracellular Signal-Regulated MAP Kinases / metabolism
Gene Expression Regulation, Neoplastic
Gene Knockdown Techniques
Genes, ras*
Humans
Immunohistochemistry
MAP Kinase Signaling System
Male
Mice
Mice, Inbred BALB C
Mice, Nude
MicroRNAs / biosynthesis
MicroRNAs / genetics*
MicroRNAs / metabolism
Nasopharyngeal Carcinoma
Nasopharyngeal Neoplasms / genetics*
Nasopharyngeal Neoplasms / metabolism
Nasopharyngeal Neoplasms / pathology*
Proto-Oncogene Proteins / antagonists & inhibitors
Proto-Oncogene Proteins / biosynthesis
Proto-Oncogene Proteins / genetics
Proto-Oncogene Proteins c-akt / antagonists & inhibitors
Proto-Oncogene Proteins c-akt / genetics
Proto-Oncogene Proteins c-akt / metabolism
Proto-Oncogene Proteins p21(ras)
Transfection
ras Proteins / antagonists & inhibitors
ras Proteins / biosynthesis
ras Proteins / genetics

Substances

3' Untranslated Regions
KRAS protein, human
MicroRNAs
Proto-Oncogene Proteins
Proto-Oncogene Proteins c-akt
Extracellular Signal-Regulated MAP Kinases
Proto-Oncogene Proteins p21(ras)
ras Proteins