The long noncoding RNA expression profile of hepatocellular carcinoma identified by microarray analysis
Ontology highlight
ABSTRACT: To explore the potential involvement of lncRNAs in hepatocellular carcinoma (HCC) oncogenesis, we conducted lncRNA and mRNA profiling in 3 pairs of human HCC and adjacent normal tissue (NT) by microarray. With abundant probes accounting for 33,045 lncRNAs and 30,215 coding transcripts in our microarray, the number of lncRNAs and coding transcripts that could be detected here is 10,149 and 14,944, respectively. From the data, thousands of lncRNAs and mRNAs were found to bedifferentially expressed (Fold Change≥2.0) in HCC tissues compared with NT and identified 624 lncRNAs and 1050 mRNAs were differentially expressed in all three HCC tissues.Bioinformatic analysis (gene ontology, pathway and network analysis) was performed for further study of these differentially expressed mRNAs.By qRT-PCR analysis in nineteen pairs HCC and adjacent normal tissues, we found that eightl ncRNAs were aberrantly expressed in HCC compared with corresponding NT, which is consistent with microarray data. Additionally, change trends of seven lncRNAs were basically identical to their nearby coding genes. In this study, to explore the potential involvement of lncRNAs in hepatocellular carcinoma (HCC) oncogenesis, we conducted lncRNA and mRNA profiling in 3 pairs of human HCC and adjacent normal tissue (NT) by microarray.
Project description:To explore the potential involvement of lncRNAs in hepatocellular carcinoma (HCC) oncogenesis, we conducted lncRNA and mRNA profiling in 3 pairs of human HCC and adjacent normal tissue (NT) by microarray. With abundant probes accounting for 33,045 lncRNAs and 30,215 coding transcripts in our microarray, the number of lncRNAs and coding transcripts that could be detected here is 10,149 and 14,944, respectively. From the data, thousands of lncRNAs and mRNAs were found to bedifferentially expressed (Fold Change≥2.0) in HCC tissues compared with NT and identified 624 lncRNAs and 1050 mRNAs were differentially expressed in all three HCC tissues.Bioinformatic analysis (gene ontology, pathway and network analysis) was performed for further study of these differentially expressed mRNAs.By qRT-PCR analysis in nineteen pairs HCC and adjacent normal tissues, we found that eightl ncRNAs were aberrantly expressed in HCC compared with corresponding NT, which is consistent with microarray data. Additionally, change trends of seven lncRNAs were basically identical to their nearby coding genes.
Project description:Although many protein-coding genes have been identified to be aberrantly expressed in hepatocellular carcinoma (HCC), the mechanisms that account for development and progression of HCC remain unclear. In recent years, long noncoding RNAs (lncRNAs) have been shown to have critical regulatory roles in mammalian cell biology. Many lncRNAs can result in aberrant expression of gene products that may contribute to cancer biology. In this study, we first identified non-overlapping signatures of a small number of lncRNAs that are aberrantly expressed in human HCC compared with paired peritumoral tissues. Then we used real-time PCR to validate five lncRNAs whose expression was altered in HCC compared with paired peritumoral tissues. Using loss-of-function and gain-of-function approaches, we found that an lncRNA (termed lncRNA-HEIH) plays a key role in cell cycle regulation. We further demonstrated that lncRNA-HEIH bound to enhancer of zeste homolog 2 (EZH2) and that this interaction was required for the repression of EZH2 target genes. Together, these results reveal insights into the molecular regulation mechanisms of HCC cell cycle regulation and lead us to propose that lncRNAs may serve as key regulatory hubs in cancer biology. A ten chip study using total RNA recovered from five separate HCC tissues and five corresponding paired non-tumor samples.
Project description:Long noncoding RNAs (lncRNAs) are a class of non-coding RNAs longer than 200 nt that function in endogenous gene regulation and tumorigenesis. Hepatocellular carcinoma (HCC) is a heterogeneous disease with different treatment outcome. It is a challenge to develop a prognostic marker to identify HCC patients who are at greatest risk for recurrence or death. In this study, we try to screen lncRNAs whose expression levels are associated with recurrence or death of HCC patients through an extensive lncRNA profiling study on a cohort of 59 HCC patients.
Project description:Long noncoding RNAs (lncRNAs) are a class of non-coding RNAs longer than 200 nt that function in endogenous gene regulation and tumorigenesis. Hepatocellular carcinoma (HCC) is a heterogeneous disease with different treatment outcome. It is a challenge to develop a prognostic marker to identify HCC patients who are at greatest risk for recurrence or death. In this study, we try to screen lncRNAs whose expression levels are associated with recurrence or death of HCC patients through an extensive lncRNA profiling study on a cohort of 59 HCC patients. For these experiments, we used RNA extracted from 59 HCC tissues and 20 normal livers. Total RNAs from the 20 normal livers were pooled and used as a reference for all microarray experiments. For each microarray experiment, Cy5-labeled probes derived from the DNase-treated total RNA from each HCC sample was hybridized against Cy3-labeled probes derived from common reference on Arraystar Human LncRNA Microarray (Arraystar, Rockville, USA). LncRNAs whose expression was significantly associated with disease-specific survival and time to recurrence were selected based on microarray data. The univariate Cox proportional hazards model was used to assess the association of lncRNAs with survival. We computed a statistical significance level (P value) for two endpointsM-bM-^@M-^Tthe time to cancer-related death and time to recurrence, based on univariate Cox proportional hazards models in BRB-ArrayTools version 4.2.0.
Project description:To explore the potential involvement of lncRNAs in pancreatic ductal adenocarcinoma (PDAC) oncogenesis, we conducted lncRNA profiling in six pairs of human PDAC and adjacent normal tissue by microarray. Our results showed that clusters of lncRNAs were aberrantly expressed in PDAC compared with normal samples, and provided potential targets for future treatment of PDAC and novel insights into PDAC biology.
Project description:To explore critical roles of lncRNA and mRNA playing in the pathogenesis of hepatocellular carcinoma, the Agilent microarray was used to simultaneously profile lncRNA and mRNA expression in 7 pairs of HCC and matched adjacent tumor-free tissues.
Project description:Recent studies show that long non-coding RNAs (lncRNAs) play crucial roles in human cancers. However, functional lncRNAs and their downstream mechanisms are largely unknown in the molecular pathogenesis of intrahepatic cholangiocarcinoma (ICC) and its progression. In the present study, we performed transcriptomic profiling of five ICC and paired adjacent noncancerous tissues (N) using lncRNA and mRNA microarrays to identify relevant biomarkers in ICC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to validate the microarray results. We sought correlations between the expression levels of lncRNAs and those of target genes. Clinicopathological characteristics and overall survival were compared using the t-test and the Kaplan–Meier method, respectively. A total of 3,054 and 2,111 lncRNAs were significantly up- and down-regulated(fold change?2, p?0.05) in ICC tissues compared to the adjacent NT samples. Bioinformatic analysis indicated that most such genes were related to carcinogenesis, hepatic system disease, and signal transduction. Positive correlations were evident between four pairs of lncRNAs and target mRNAs (RNA43085 and SULF1, RNA47504 and KDM8, RNA58630 and PCSK6, and RNA40057 and CYP2D6). In addition, some lncRNAs and mRNAs were significantly associated with clinicopathological characteristics. The cumulative overall survival rate was significantly associated with low-level expression of CYP2D6 (p=0.005) and PCSK6 (p=0.038). And patients with high expression levels of CYP2D6 and RNA40057 have significant better prognosis (p=0.014). Our results suggested that lncRNA expression profile in ICC tissues is profoundly different from that in NT samples. The lncRNA signature could be used as a biomarker for the prognosis of patients with ICC. Furthermore, the combination of lncRNA and mRNA can reliably predict the survival. The lncRNA expression profiles of cancer and adjacent normal tissues form 5 ICC patients were studied by microarray and an combination of lncRNA and mRNA could be used as a biomarker for the prognosis of patients with ICC
Project description:Objective: The aim of this study was to reveal the function of the long non-coding RNA (lncRNA) RP11-556E13.1 (RP11) and its clinical significance in hepatocellular carcinoma. Methods: LncRNA and mRNA expression profiling was performed using lncRNA and mRNA microarrays in 5 pairs of HCC and adjacent tissues. 112 paired HCC and adjacent tissue samples were analyzed by semiquantitative real-time polymerase chain reaction (sqRT-PCR) to evaluate the expression of RP11 and its possible associated clinical significance. Smart silencer RNA (siRNA) was used to knockdown the expression of RP11 in HCC cells. After knockdown, the function of RP11 was determined in vitro using some kinds of cell functional experiments in HCC cells including cell proliferation assay, cell apoptosis assay and cell cycle assay. Western blotting (WB) was performed to detect proteins that were presumably associated with these functional changes. An Affymetrix Human HTA2.0 microarray was used to detect differentially expressed genes in HCC cells after RP11 knockdown. GO enrichment and KEGG pathway enrichment analysis were then performed to elucidate the biological roles of these differentially expressed mRNAs.
Project description:Many protein-coding oncofetal genes are highly expressed in murine and human fetal liver and silenced in adult liver. The protein products of these hepatic oncofetal genes have been used as clinical markers for the recurrence of hepatocellular carcinoma (HCC) and as therapeutic targets for HCC. Herein, we examined the expression profiles of long non-coding RNAs (lncRNAs) and mRNAs found in fetal and adult liver in mice.LncRNA-mPvt1 is an oncofetal RNA that was found to promote cell proliferation, cell cycling and the expression of stem cell-like properties of murine cells. Human lncRNA-hPVT1 promotes cell proliferation, cell cycling and the acquisition of stem cell-like properties in HCC cells by stabilizing NOP2 protein. Regulation of the lncRNA-hPVT1/NOP2 pathway may have beneficial effects in the treatment of HCC. We collected mouse fetal livers (E12.5, E14.5, E17.5 days), neonatal murine livers and adult murine livers (8 weeks). The total RNAs recovered from these developmental livers and were used to acquire different expression profiles of mRNAs and lncRNAs.
Project description:The expression of long non-coding RNAs - lncRNAs - was profiled in the liver cancer Hepatocellular Carcinoma - HCC - and in normal liver tissues using the Invitrogen NCode Human lncRNA Array Platform.