ABSTRACT
Objective To investigate whether the long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) can act as a competitive endogenous RNA (ceRNA) to promote the migration of hepatocellular carcinoma (HCC) cells.Methods Transient transfection of small interfering RNA (siRNA) against MALAT1 was used to knockdown MALAT1 in HepG2 cells.Transwell assays were employed to assess the migration capabilities of HepG2 cells upon MALAT1 knockdown.RNA pull-down assays were performed to validate the direct binding between MALAT1 and miR-126*.Quantitative reverse transcription PCR (qRT-PCR) and Western blotting assays were used to detect the mRNA and protein levels of the miR-126* target genes.The dysregulation and prognostic significance of MALAT1 and miR-126* were analyzed in the public dataset of The Cancer Genome Atlas (TCGA).Results Compared with the control group, MALAT1 knockdown significantly inhibited the migration of HCC cells.MALAT1, with three miR-126* response elements, directly sponged miR-126* in a sequence-specific manner.The mRNA and protein levels of CXCL12, which was the miR-126* target gene, were significantly down-regulated upon MALAT1 knockdown.The TCGA database showed that MALAT1 was significantly up-regulated in HCC and high expression levels of MALAT1 were significantly associated with poor disease-free survival, whereas an opposite pattern of miR-126* was observed.Conclusion This study suggests that MALAT1 directly sponges miR-126* and upregulates the expression of CXCL12, which in turn promotes the migration of HCC cells.
ABSTRACT
Genomic polymorphisms come in various forms including single nucleotide variations, translocations, insertions and copy number variations (CNVs). As a form of structural variation, the CNVs comprise common and rare forms based on their populational frequencies. Studies have demonstrated that certain CNVs are associated with risks for neuro-developmental diseases, viral infections, chronic inflammations, and cancers. With the development of high-resolution genome typing technologies such as microarrays and whole genome sequencing, the human genomic CNVs map has been continuously improved and refined. In-depth study of CNVs not only can provide comprehensive understanding for their structural variations and genetic evolution, but also provide new insights into genetic factors contributing to such diseases. In this paper, the general characteristics, pathogenesis and detection methods for the CNVs, as well as their association with human diseases are reviewed.
Subject(s)
Humans , DNA Copy Number Variations , Genetic Predisposition to DiseaseABSTRACT
Hepatocellular carcinoma ( HCC) , as one of the most common malignant neoplasms , has a relatively high morbidity and mortality rate worldwide.MicroRNAs (miRNAs),a type of comparatively conserved endogenous small non-coding RNAs, function as pivotal regulators involved in various biological functions through the post -transcriptional regulation of gene expression .Some miRNA genes are arranged into a intandem model and reside close together on the same chromosome , forming miRNA clusters . These clustered miRNAs are mostly located on polycistronic transcripts and expressed at similar levels.In the human imprinted 14q32 region, 52 miRNA genes are organized as a large cluster which spans about 220 kb of the long arm ( q) .Lines of evidence show that dysregulation of miRNAs in this cluster are involved in the development of HCC .This review summarizes the structural characteristics of 14 q32 miRNA cluster as well as its impact on HCC in initiation and progression .