p42.3 is a novel gene that has been recently isolated and identified by the mRNA differential display (mRNADD) technique. The full-length cDNA of p42.3 is approximately 4.0 kb, and the gene encodes a 389 amino acid (aa) protein that is estimated to have a molecular mass of 42.3 kDa. Further research has revealed that its expression is cell cycle-dependent in gastric cancer (GC) cell lines. Its protein expression peaks during the M phase of the cell cycle, before gradually decreasing after cell division; this indicates that p42.3 may be involved in cell cycle regulation. Furthermore, silencing of p42.3 by small interfering RNA (siRNA) results in the upregulation of CHK2 and the downregulation of cyclin B1, which are two key proteins involved in cell cycle regulation 
. While RT-PCR and immunohistochemical analyses have shown that p42.3 is upregulated in GC compared with normal tissue samples, functional research has suggested that the depletion of p42.3 may not only result in the inhibition of GC cell proliferation and colony formation in vitro
, but may also significantly reduce tumorigenicity in nude mice 
. Although previous studies have suggested a critical role for the p42.3 gene in the pathology of GC, the specific underlying mechanisms of its action remain to be clarified.
MicroRNAs (miRNAs) consist of a class of small (~22 nucleotides), endogenous, non-coding RNAs that are known to play important regulatory roles in gene expression 
. The primary miRNA transcript is called pri-miRNA 
, which is transcribed by RNA polymerase II or III 
. The pri-miRNA is then cleaved by the Drosha-DGCR8 microprocessor complex to produce the precursor hairpin molecule (pre-miRNA) which is then exported from the nucleus to the cytoplasm by exportin−5/Ran-GTP. With the assistance of a complex that contains the RNase Dicer and the double-stranded RNA-binding protein, TRBP, the ~70-nucleotide pre-miRNA is processed into mature miRNA 
. The functional strand of the mature miRNA is loaded into the RNA-induced silencing complex (RISC), which contains the proteins, argonaute (Ago) and Tnrc6, while the other strand is usually degraded 
. The mature miRNA guides the RISC to the imperfect complementary sequences in target mRNAs to repress the cognate mRNA translation, promote transcript decay, or both 
. It is estimated that most coding genes are probably regulated by miRNAs and, whilst a miRNA may regulate more than one target genes, certain genes can be regulated by multiple miRNAs 
Growing evidence suggests that miRNAs are involved in a wide range of physiological and pathological processes, including development, differentiation, proliferation and apoptosis [12.13,14,15]. Although abnormalities of miRNA expression have been determined in many human tumors, including colorectal, gastric and breast cancers 
, the number of such tumors is still expanding. However, the detailed functions of miRNA in tumors remain to be elucidated.
Recent studies have suggested that miR-29 has complex functions in various diseases. MiR-29a may behave as a tumor suppressor in both lung and pancreatic cancer cell lines, and thus the exogenous overexpression of miR-29a results in a significant reduction in the invasive potential and proliferation of these cell lines 
. The tumor suppressor role of miR-29a is also supported by its observed downregulation in a broad spectrum of solid tumors, including neuroblastoma, sarcomas and brain tumors 
. In contrast, miR-29a is upregulated in indolent human B-cell chronic lymphocytic leukemia (B-CLL) 
and acute myeloid leukemia (AML) 
, which suggests a possible tumor promoter role. In addition, the aberrant expression of miR-29a can be found in many non-malignant diseases, including liver fibrosis 
, diabetes 
and Alzheimer’s disease 
. Although many genes have already been confirmed to be the direct targets of miR-29a, such as PPM1D 
, PI3K 
and neuron navigator 3 
, they represent a very small fraction of the total genes that miR-29a targets.
In the present report, we demonstrate that p42.3 expression was controlled at the levels of both mRNA and protein by miR-29a via direct targeting of the 3’UTR of p42.3. MiR-29a could suppress cell proliferation and induce cell cycle arrest, at least in part, via the downregulation of p42.3 expression. Moreover, we found that the expression of p42.3 protein was inversely correlated with miR-29a expression in human GC tissues.