ABSTRACT
MicroRNAs (miRNAs) are conserved small non-coding RNAs that play an important role in the regulation of gene expression and participate in a variety of biological processes. The biogenesis of miRNAs is tightly controlled at multiple steps, such as transcription of miRNA genes, processing by Drosha and Dicer, and transportation of precursor miRNAs (pre-miRNAs) from the nucleus to the cytoplasm by exportin-5 (XPO5). Given the critical role of nuclear export of pre-miRNAs in miRNA biogenesis, any alterations of XPO5, resulting from either genetic mutation, epigenetic change, abnormal expression level or posttranslational modification, could affect miRNA expression and thus have profound effects on tumorigenesis. Importantly, XPO5 phosphorylation by ERK kinase and its cis/trans isomerization by the prolyl isomerase Pin1 impair XPO5's nucleo-to-cytoplasmic transport ability of pre-miRNAs, leading to downregulation of mature miRNAs in hepatocellular carcinoma. In this review, we focus on how XPO5 transports pre-miRNAs in the cells and summarize the dysregulation of XPO5 in human tumors.
Subject(s)
Humans , Carcinoma, Hepatocellular , Genetics , Metabolism , Cell Nucleus , Metabolism , Cytoplasm , Metabolism , Karyopherins , Chemistry , Metabolism , Physiology , Liver Neoplasms , Genetics , Metabolism , MicroRNAs , Chemistry , Metabolism , NIMA-Interacting Peptidylprolyl Isomerase , Neoplasms , Genetics , Metabolism , RNA Precursors , Chemistry , Metabolism , RNA TransportABSTRACT
Objective To investigate the expression of miR?126, miR?355 and exportin?5 in lung cancer. Methods The cancer tissue and the tissue adjacent to carcinoma of 47 cases of patients with lung cancer was used to detect the expression of miR?126, miR?355 and Exportin?5 by the real?time fluorescence quantitative PCR. Results Significant difference of the expression of miR?126 (t=2.02,P=0.03) and exportin?5 (t=4.62,P<0.01) was observed in lung cancer tissue and tissue adjacent to carcinoma. Mature miR?126 and pri?miR?126 (R=0.309 , P = 0.044) had a negative correlation in the tissue adjacent to carcinoma. In the cancer tissue,miR?126 and MRP (R=0.432, P=0.019), miR?335 and k167 (R=0.410, P=0.033) were positively correlated, however, exportin?5 and TOPO (R=0.357, P=0.045), the pri?miR?126 and drinking (R=0.340, P=0.024), the pri?miR?126 and MRP (R=0.427, P=0.027) had a negative correlation relationship. Conclusion Expression of miR?126 and exportin?5 was decreased in lung cancer tissue, which may contribute to the occurrence and development of lung cancer.