title: MiR-23a in amplified 19p13.13 loci targets metallothionein 2A and promotes growth in gastric cancer cells.
abstract: Copy number variation (CNV) and abnormal expression of microRNAs (miRNAs) always lead to deregulation of genes in cancer, including gastric cancer (GC). However, little is known about how CNVs affect the expression of miRNAs. By integrating CNV and miRNA profiles in the same samples, we identified eight miRNAs (miR-1274a, miR-196b, miR-4298, miR-181c, miR-181d, miR-23a, miR-27a and miR-24-2) that were located in the amplified regions and were upregulated in GC. In particular, amplification of miR-23a-27a-24-2 cluster and miR-181c-181d cluster frequently occurred at 19p13.13 and were confirmed by genomic real-time PCR in another 25 paired GC samples. Moreover, in situ hybridization (ISH) experiments represented that mature miR-23a was increased in GCs (75.5%, 40/53) compared with matched normal tissues (28.6%, 14/49, P = 0.001). Knocking down of miR-23a expression inhibited BGC823 cell growth in vitro and in vivo. In addition, the potential target genes of miR-23a were investigated by integration of mRNA profile and miRNA TargetScan predictions, we found that upregulation of miR-23a and downregulation of metallothionein 2A (MT2A) were detected simultaneously in 70% (7/10) of the miRNA and mRNA profiles. Furthermore, an inverse correlation between miR-23a and MT2A expression was detected in GCs and normal tissues. Through combining luciferase assay, we confirmed that MT2A is a potential target of miR-23a. In conclusion, these results suggest that integration of CNV-miRNA-mRNA profiling is a powerful tool for identifying molecular signatures, and that miR-23a might play a role in regulating MT2A expression in GC.
authors.affiliation: Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research Ministry of Education, Peking University Cancer Hospital/Institute, Beijing, 100142, P.R., China.
authors.forename: Juan
authors.initials: J
authors.lastname: An
authors.forename: Yuanming
authors.initials: Y
authors.lastname: Pan
authors.forename: Zhi
authors.initials: Z
authors.lastname: Yan
authors.forename: Wenmei
authors.initials: W
authors.lastname: Li
authors.forename: Jiantao
authors.initials: J
authors.lastname: Cui
authors.forename: Jiao
authors.initials: J
authors.lastname: Yuan
authors.forename: Liqing
authors.initials: L
authors.lastname: Tian
authors.forename: Rui
authors.initials: R
authors.lastname: Xing
authors.forename: Youyong
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019295:Computational Biology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008668:Metallothionein / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D060888:Real-Time Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism*
chemical_list: C552430:MIRN23a microRNA, human; C491053:MT2A protein, human; D035683:MicroRNAs; D008668:Metallothionein
keywords: COPY NUMBER VARIATION; GASTRIC CANCER; MT2A; miR-23a