MicroRNA 29c is down-regulated in nasopharyngeal carcinomas, up-regulating mRNAs encoding extracellular matrix proteins.
Using highly sensitive microarray-based procedures, we identified eight microRNAs (miRNAs) showing robust differential expression between 31 laser-capture-microdissected nasopharyngeal carcinomas (NPCs) and 10 normal healthy nasopharyngeal epithelial samples. In particular, miRNA mir-29c was expressed at one-fifth the levels in tumors as in normal epithelium. In NPC tumors, the lower mir-29c levels correlated with higher levels of multiple mRNAs whose 3' UTRs can bind mir-29c at target sequences conserved across many vertebrates. In cultured cells, introduction of mir-29c down-regulated these genes at the level of mRNA and inhibited expression of luciferase encoded by vectors having the 3' UTRs of these genes. Moreover, for each of several genes tested, mutating the mir-29c target sites in the 3' UTR abrogated mir-29c-induced inhibition of luciferase expression. Most of the mir-29c-targeted genes identified encode extracellular matrix proteins, including multiple collagens and laminin gamma1, that are associated with tumor cell invasiveness and metastatic potential, prominent characteristics of NPC. Thus, we identify eight miRNAs differentially expressed in NPC and demonstrate the involvement of one in regulating genes involved in metastasis.
Sengupta
Srikumar
S
Institute for Molecular Virology, Howard Hughes Medical Institute, McArdle Laboratory for Cancer Research, Departments of Statistics and Biostatistics and Medical Informatics, University of Wisconsin, Madison, WI 53076, USA.
den Boon
Johan A
JA
Chen
I-How
IH
Newton
Michael A
MA
Stanhope
Stephen A
SA
Cheng
Yu-Juen
YJ
Chen
Chien-Jen
CJ
Hildesheim
Allan
A
Sugden
Bill
B
Ahlquist
Paul
P
D016022:Case-Control Studies; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000502:physiology; D009303:Nasopharyngeal Neoplasms / Q000235:genetics*; D012333:RNA, Messenger; D015854:Up-Regulation
D016326:Extracellular Matrix Proteins; C532045:MIRN29a microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger