Highly deregulated lncRNA LOC is associated with overall worse prognosis in Hepatocellular Carcinoma patients (original) (raw)
Related papers
Scientific Reports, 2020
Long non-coding RNAs (lncRNAs) are often aberrantly expressed in Hepatocellular Carcinoma (HCC). We hypothesize that lncRNAs modulate HCC prognoses through differential deregulation of key lncRNAs affecting important gene network in key cancer pathways associated with pertinent clinical phenotype. Here, we present a novel approach integrating lncRNA-mRNA expression profiles with clinical characteristics to identify lncRNA signatures in clinically-relevant co-expression lncRNA-mRNA networks residing in pertinent cancer pathways. Notably one network, associated with poorer prognosis, comprises five up-regulated lncRNAs significantly correlated (|Pearson Correlation Coefficient|≥ 0.9) with 91 up-regulated genes in the cell-cycle and Rho-GTPase pathways. All 5 lncRNAs and 85/91 (93.4%) of the correlated genes were significantly associated with higher tumor-grade while 3/5 lncRNAs were also associated with no tumor capsule. Interestingly, 2/5 lncRNAs that are correlated with numerous gen...
The Landscape of lncRNAs in Hepatocellular Carcinoma: A Translational Perspective
Cancers, 2021
LncRNAs are emerging as relevant regulators of multiple cellular processes involved in cell physiology as well as in the development and progression of human diseases, most notably, cancer. Hepatocellular carcinoma (HCC) is a prominent cause of cancer-related death worldwide due to the high prevalence of causative factors, usual cirrhotic status of the tumor-harboring livers and the suboptimal benefit of locoregional and systemic therapies. Despite huge progress in the molecular characterization of HCC, no oncogenic loop addiction has been identified and most genetic alterations remain non-druggable, underscoring the importance of advancing research in novel approaches for HCC treatment. In this context, long non-coding RNAs (lncRNAs) appear as potentially useful targets as they often exhibit high tumor- and tissue-specific expression and many studies have reported an outstanding dysregulation of lncRNAs in HCC. However, there is a limited perspective of the potential role that dere...
Recurrently deregulated lncRNAs in hepatocellular carcinoma
Nature Communications, 2017
Hepatocellular carcinoma (HCC) cells often invade the portal venous system and subsequently develop into portal vein tumour thrombosis (PVTT). Long noncoding RNAs (lncRNAs) have been associated with HCC, but a comprehensive analysis of their specific association with HCC metastasis has not been conducted. Here, by analysing 60 clinical samples' RNA-seq data from 20 HCC patients, we have identified and characterized 8,603 candidate lncRNAs. The expression patterns of 917 recurrently deregulated lncRNAs are correlated with clinical data in a TCGA cohort and published liver cancer data. Matched array data from the 60 samples show that copy number variations (CNVs) and alterations in DNA methylation contribute to the observed recurrent deregulation of 235 lncRNAs. Many recurrently deregulated lncRNAs are enriched in co-expressed clusters of genes related to cell adhesion, immune response and metabolic processes. Candidate lncRNAs related to metastasis, such as HAND2-AS1, were further validated using RNAi-based loss-of-function assays. Thus, we provide a valuable resource of functional lncRNAs and biomarkers associated with HCC tumorigenesis and metastasis.
Emerging role of lncRNA in cancer: a potential avenue in molecular medicine
Annals of Translational Medicine, 2016
Hepatocellular carcinoma (HCC) accounts for the second largest number of cancer related deaths globally with limited management options for the advanced disease. Although substantial research has identified molecular targets, with strong validation in pre-clinical in vivo studies, translation of therapeutics to clinics has shown modest success. In a recent manuscript in Hepatology, Zhou and Yang et al. unravel a novel p53 associated long noncoding RNA (PRAL) as a potential prognostic marker and molecular target in HCC. Their work provides a promising approach at capitalizing the tumor suppressive role of p53 protein in fighting HCC. More importantly, it emphasizes the evolving significance of long non-coding RNAs (lncRNA) in molecular medicine. Current research trends focus on identifying and understanding roles of lncRNA in regulation of gene expression relevant to multiple disease pathophysiologies thereby presenting a new avenue of research in molecular and translational medicine.
2016
Hepatocellular carcinoma (HCC) are highly potent to invade the portal venous system and subsequently develop into the portal vein tumor thrombosis (PVTT). PVTT could induce intrahepatic metastasis, which is closely associated with poor prognosis. A comprehensive systematic characterization of long noncoding RNAs (lncRNAs) associated with HCC metastasis has not been reported. Here, we first assayed 60 clinical samples (matched primary tumor, adjacent normal tissue, and PVTT) from 20 HCC patients using total RNA sequencing. We identified and characterized 8,603 novel lncRNAs from 9.6 billion sequenced reads, indicating specific expression of these lncRNAs in our samples. On the other hand, the expression patterns of 3,212 known and novel recurrently deregulated lncRNAs (in >=20% of our patients) were well correlated with clinical data in a TCGA cohort and published liver cancer data. Some lncRNAs (e.g., RP11-166D19.1/MIR100HG) were shown to be useful as putative biomarkers for prog...
Cancers, 2015
Long non-coding RNAs (lncRNAs) are larger than 200 nucleotides in length and pervasively expressed across the genome. An increasing number of studies indicate that lncRNA transcripts play integral regulatory roles in cellular growth, division, differentiation and apoptosis. Deregulated lncRNAs have been observed in a variety of human cancers, including hepatocellular carcinoma (HCC). We determined the expression profiles of 90 lncRNAs for 65 paired HCC tumor and adjacent non-tumor tissues, and 55 lncRNAs were expressed in over 90% of samples. Eight lncRNAs were significantly down-regulated in HCC tumor compared to non-tumor tissues (p < 0.05), but no lncRNA achieved statistical significance after Bonferroni correction for multiple comparisons. Within tumor tissues, carrying more aberrant lncRNAs (6-7) was associated with a borderline significant reduction Cancers 2015, 7 1848 in survival (HR = 8.5, 95% CI: 1.0-72.5). The predictive accuracy depicted by the AUC was 0.93 for HCC su...
LncRNAs as novel players in hepatocellular carcinoma recurrence
Oncotarget, 2018
Long non-coding RNAs (lncRNAs) are ncRNAs more than 200 nucleotides long that participate to a wide range of biological functions. However, their role in cancer is poorly known. By using an NGS-based approach we analyzed the intragenic and poliA-lncRNAs in hepatocellular carcinoma (HCC) and we assayed the relationships between their deregulated expression and clinical-pathological characteristics. The expression profile of lncRNAs was studied in a discovery series of 28 HCC and matched cirrhosis and was validated in an independent cohort of 32 HCC patients both in tissue and serum. The correlation between lncRNA expression and clinical-pathological variables, EMT markers and putative sponged microRNAs level were investigated. Functional experiments were performed in HCC-derived cell lines to clarify the role of selected lncRNAs in HCC. A panel of deregulated lncRNAs differentiated HCC from cirrhotic tissue. CASC9 and LUCAT1 were up-regulated in a subset of HCC-derived cell lines and in half of HCCs which displayed a lower recurrence after surgery. LUCAT1 and CASC9 silencing increased cell motility and invasion capability in HCC cells and influenced the EMT phenotype. LUCAT1 was demonstrated to directly sponge the onco-miR-181d-5p. Both LUCAT1 and CASC9 were secreted in exosomes, and higher circulating CASC9 levels were associated with tumor size and HCC recurrence after surgery, suggesting its potential usage as putative non-invasive prognostic biomarker of recurrence.
LncRNA HANR Promotes Tumorigenesis and Increase of Chemoresistance in Hepatocellular Carcinoma
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2017
Hepatocellular carcinoma (HCC) is the fifth most common cancer in the world and the third leading cause of cancer-related death. Critical roles for long non-coding RNAs (lncRNAs) have recently been demonstrated for a variety of cancers, including hepatocellular carcinoma. However, the effect and mechanism of lncRNAs in HCC tumorigenesis and chemoresistance have not been extensively characterized. In the current study, we have identified a HCC-expressed lncRNA termed as HANR (HCC associated long non-coding RNA). We identified HANR by microarray analysis and validated its up-regulated expression by quantitative PCR. RNA pull-down and pathway analyses were conducted to evaluate physical and functional interactions with HANR. In vivo experiments were performed to assess tumorigenesis and increase of chemoresistance. In addition, the HANR expression in HCC specimens was detected by FISH. Xenograft and orthotopic mice model was constructed to observe the effect of HANR on tumorigenesis an...
lncRNAs in Hallmarks of Cancer and Clinical Applications
Non-Coding RNAs [Working Title], 2019
Long noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides in length that, in general, do not appear to have protein-coding potential. lncRNAs act in gene regulation involved with several biological processes. Furthermore, lncRNAs have been associated with a significant number of cancers, suggesting a potential role in tumorigenesis and progression. For example, HOTAIR regulates proliferation processes and other lncRNAs like highly upregulated in liver cancer (HULC), H19, PTENP1, HEIH, and antisense noncoding RNA in the INK4 locus (ANRIL). Other lncRNAs as AFAP1-AS1 and lincRNA-p21 can interact with BCL-2 and TP53, acting in apoptosis. Moreover, NORAD plays a vital role in genomic stability. Additionally, due to deregulated expression and high tissue specificity level, lncRNAs exhibit great potential as prognostic markers. In this chapter, we review the most highlighted lncRNAs acting in hallmarks of cancer and clinical application.
The Role of Long Non-Coding RNAs in Hepatocarcinogenesis
International Journal of Molecular Sciences
Whole-transcriptome analyses have revealed that a large proportion of the human genome is transcribed in non-protein-coding transcripts, designated as long non-coding RNAs (lncRNAs). Rather than being "transcriptional noise", increasing evidence indicates that lncRNAs are key players in the regulation of many biological processes, including transcription, post-translational modification and inhibition and chromatin remodeling. Indeed, lncRNAs are widely dysregulated in human cancers, including hepatocellular carcinoma (HCC). Functional studies are beginning to provide insights into the role of oncogenic and tumor suppressive lncRNAs in the regulation of cell proliferation and motility, as well as oncogenic and metastatic potential in HCC. A better understanding of the molecular mechanisms and the complex network of interactions in which lncRNAs are involved could reveal novel diagnostic and prognostic biomarkers. Crucially, it may provide novel therapeutic opportunities to add to the currently limited number of therapeutic options for HCC patients. In this review, we summarize the current status of the field, with a focus on the best characterized dysregulated lncRNAs in HCC.