LncRNA Information
ID EL0600 Name HULC Aliases HCCAT1; LINC00078; NCRNA00078
Species Homo sapiens Chromosome 6 Start site 8652137
End site 8653846 Chain plus Exon NO. 2
Assembly Ensembl Release 89 Class lincRNA NCBI accession NR_004855
Ensembl ENSG00000251164 Sequence


Disease
Disease Method Sample Expression pattern Dysfunction type Description PMID Source
diffuse large B-cell lymphoma in a cohort of DLBCL DLBCL tissues and cell lines up-regulated N/A HULC was closely related to DLBCL characteristics 27044827
papillary thyroid carcinoma microarray, qPCR etc. papillary thyroid carcinoma tissue up-regulated expression Expression profiles of five lnc-RNAs (MEG3, HULC, HOTAIR, NEAT1, and MALAT-1) previously shown to be involved in cancer metastasis were detected by qPCR in 5 pairs of papillary thyroid cancer and 11 matched lymph node metastatic tissues. Among the five, MEG3 showed significant down-expression. Overexpression of MEG3 inhibits thyroid cancer cell migration and invasion. 25997963 Lnc2Cancer
hepatocelluar carcinoma microarray, qPCR, knockdown etc. cell lines (HepG2, Huh7 etc.) up-regulated N/A The relative expression level of HULC, as determined by qPCR, was about 8-fold higher in HCC samples than in normal liver tissue. Depletion of IGF2BP1 led to an increased HULC half-life and higher steady-state expression levels, indicating a post-transcriptional regulatory mechanism. Importantly, HULC represents the first IGF2BP substrate that is destabilized. To elucidate the mechanism by which IGF2BP1 destabilizes HULC, the CNOT1 protein was identified as a novel interaction partner of IGF2BP1. CNOT1 is the scaffold of the human CCR4-NOT deadenylase complex, a major component of the cytoplasmic RNA decay machinery. Indeed, depletion of CNOT1 increased HULC half-life and expression. Thus, IGF2BP1 acts as an adaptor protein that recruits the CCR4-NOT complex and thereby initiates the degradation of the lncRNA HULC. 23728852 Lnc2Cancer
hepatocelluar carcinoma microarray, qPCR, Northern blot, ISH, knockdown etc. HCC tissue, blood up-regulated expression Highly up-regulated in liver cancer. 17241883 LncRNADisease Lnc2Cancer
prostate cancer microarray, RNA-seq, qPCR, Northern bolt, knockdown etc. prostate cancer tissue, cell lines (LNCaP, CWR22Rv1, PC3 etc.) up-regulated N/A Interestingly, nine out of these thirteen known cancer-related lncRNA showed significantly differential expression between tumor and normal prostate samples. Several lncRNA such as NEAT1, DANCR, HOTTIP, PRINS, and EGOT that have established functions in forming nuclear speckles, in development or in autoimmune disease, but were not previously known to be related to cancer, showed differential expression between tumor and normal prostate samples, suggesting their potential function in prostate cancer. 23728290 Lnc2Cancer
glioma N/A glioma patient tissues up-regulated N/A positively correlated with grade dependency in glioma patient tissues 26894862
atherosclerosis N/A liver cancer up-regulated N/A HULC regulated TNF-α-induced apoptosis through regulation of miR-9 expression 26981838
hepatocelluar carcinoma N/A N/A N/A expression A similar genome-wide differential expression screen in hepatocellular carcinoma (HCC) has uncovered another cancer-associated lncRNA, Highly Upregulated in Liver Cancer, or HULC. 20951849 LncRNADisease
hepatocelluar carcinoma N/A N/A N/A expression The lncRNA HULC is one of the most upregulated of all genes in hepatocellular carcinoma. 21802130 LncRNADisease
hepatocelluar carcinoma N/A N/A N/A expression Dysregulation and functional roles of lncRNAs in HCC 24183851 LncRNADisease
hepatocelluar carcinoma N/A N/A N/A regulation Here we focus on two best-characterized lncRNAs-HULC and LALR, which can impact proliferation through targeting various key regulators in different pathways. 24296588 LncRNADisease
hepatocelluar carcinoma N/A N/A N/A regulation Moreover, HULC correlated with upregulated hepatitis B virus X protein (HBx) that importantly contributes to HCC and that was able to promote HULC expression. The HULC-mediated downregulation of the tumor suppressor p18 supported the HCC proliferation. 24531795 LncRNADisease
liver cancer N/A N/A N/A expression The highly upregulated lncRNA HULC in liver cancer was found in the blood of HCC patients, promising a potential biomarker. 24531795 LncRNADisease
liver cancer N/A N/A N/A N/A PCGEM1, PCA3 (prostate cancer antigen 3, known also as DD3, differential display code 3) and PCNCR1 (prostate cancer ncRNA 4) are involved in prostate cancer, while HULC (highly up-regulated in liver cancer) is involved with liver cancer. 24667321 LncRNADisease
hepatocelluar carcinoma N/A N/A N/A regulation A lncRNA, highly upregulated in liver cancer (HULC), was found to contribute to tumorigenesis of HCC. 24757675 LncRNADisease
colorectal cancer qPCR etc. cell lines (HepG2, Hep3B, SKOV3 etc.) up-regulated expression HULC expression is not confined to HCC, but also to those colorectal carcinomas that metastasize to the liver. 19445043 LncRNADisease Lnc2Cancer
hepatocelluar carcinoma qPCR etc. HCC tissue up-regulated N/A In this study, we demonstrate that HULC expression is significantly higher in HCC tumors compared to normal liver tissues. Among the tumor tissues, higher HULC expression is positively associated with Edmondson histological grades or with hepatitis B (HBV) positive status. Moreover, HULC lncRNA is detected with higher frequency in the plasma of HCC patients compared to healthy controls. Higher HULC detection rates are observed in the plasma of patients with higher Edmondson grades or with HBV+ status. 23762823 Lnc2Cancer
osteosarcoma qPCR etc. osteosarcoma tissue, cell lines(MG-63, U2OS, SAOS-2 etc.) up-regulated expression In the present study, we demonstrated that HULC was significantly up-regulated in osteosarcoma tissues and cell lines compared with normal controls, and over-expression of HULC was correlated with clinical stage and distant metastasis. Moreover, higher HULC expression was associated with shorter overall survival of osteosarcoma patients.e, decreased expression of HULC markedly suppressed osteosarcoma cell proliferation, migration, and invasion. 26045809 Lnc2Cancer
gastric cancer qPCR etc. gastric cancer tissue, cell lines(AGS, MKN45, 7901 etc.) up-regulated expression All the 8 lncRNAs were then subjected to qPCR validation using 20 pairs of GC and control tissues. Among them, HOTAIR, PVT1, H19, MALAT1, GHET1 and HULC were significantly higher in tumor tissues compared with control tissues. 26096073 Lnc2Cancer
hepatocelluar carcinoma qPCR etc. blood (plasma), HCC tissue up-regulated expression Circulating HULC and Linc00152 were significantly up-regulated in plasma samples of HCC patients during training set and validation set. 26356260 Lnc2Cancer
pancreatic cancer qPCR, knockdown etc. pancreatic cancer tissue, cell lines (MIAPace-2, CFPAC-1, PANC-1, AsPC-1 etc.) up-regulated expression The higher expression of HULC was significantly correlated with large tumor size, advanced lymph node metastasis and vascular invasion. Multivariate analyses revealed that HULC expression served as an independent predictor for overall survival. Further experiments revealed that HULC knockdown significantly repressed cell proliferation of PC in vitro. 25412939 Lnc2Cancer
liver cancer qPCR, Luciferase reporter assay, Western blot etc. liver cancer tissue, cell lines (CREB, HULC, Prkacb etc.) up-regulated expression Long non-coding RNA (lncRNA), highly up-regulated in liver cancer (HULC) plays an important role in tumorigenesis. Depletion of HULC resulted in a significant deregulation of several genes involved in liver cancer. Although up-regulation of HULC expression. 20423907 LncRNADisease Lnc2Cancer
gastric cancer qPCR, Western blot etc. gastric cancer tissue, cell lines (GES-1, SGC7901, MKN28, MKN45, AGS, BGC823 etc.) up-regulated N/A In the present study, we demonstrated that HULC was significantly overexpressed in GC cell lines, compared with normal controls, and this overexpression was correlated with lymph node metastasis, distant metastasis and advanced tumor node metastasis stages.Additionally, HULC contributed to the malignant phenotype of GC cells through its regulation of diverse cellular processes, including proliferation, apoptosis, migration and invasion. 24247585 Lnc2Cancer
hepatocelluar carcinoma qPCR, Western blot, knockdown etc. cell lines (MHCC97L, HepG2, cHL-7702) up-regulated expression The expression of HEIH and HULC in hepatocellular carcinoma cell line was significantly increased compared with human normal hepatocyte line (P<0.05). The expression of HULC in HepG2 was higher than that in MHCC97L. The over-expression of HULC could enhance proliferation of MHCC97L and HepG2, however, the over-expression of HEIH could not. The over-expression of HULC and HEIH could promote invasion of MHCC97L and HepG2. Invasion of MHCC97L and HepG2 did not have significant change after down-regulating of HEIH and HULC by siRNA. Over-expression of HULC up-regulated the expression of Snail in HepG2. 26550214 Lnc2Cancer
liver cancer qPCR, Western blot, knockdown, ChIP, Luciferase reporter assay etc. HCC tissue, cell lines (HepG2, Huh7, HepG2.2.15 etc.) up-regulated interaction Levels of HULC were positively correlated with levels of SPHK1 and its product, sphingosine-1-phosphate (S1P), in patients HCC samples. HULC increased SPHK1 in hepatoma cells. Mechanistically, HULC activated the promoter of SPHK1 in hepatoma cells through the transcription factor E2F1. Chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assay (EMSA) further showed that E2F1 was capable of binding to the E2F1 element in the SPHK1 promoter. HULC increased the expression of E2F1 in hepatoma cells and levels of HULC were positively correlated with those of E2F1 in HCC tissues. Intriguingly, HULC sequestered miR-107, which targeted E2F1 mRNA 3'UTR, by complementary base pairing. Functionally, si-SPHK1 remarkably abolished the HULC-enhanced tumor angiogenesis in vitro and in vivo. Taken together, we conclude that HULC promotes tumor angiogenesis in liver cancer through miR-107/E2F1/SPHK1 signaling. 26540633 Lnc2Cancer
hepatocellular carcinoma qPCR, Western blot, Luciferase reporter assay etc. HCC tissue, cell lines (L-O2 cell line, L-O2-X) up-regulated expression Our data show that an lncRNA, HULC, is responsible for the perturbations in circadian rhythm through upregulating circadian oscillator CLOCK in hepatoma cells, resulting in the promotion of hepatocarcinogenesis. Mechanistically, the complementary base pairing between HULC and the 5'untranslated region of CLOCK mRNA underlay the HULC-modulated expression of CLOCK, and the mutants in the complementary region failed to achieve the event. 25622901 Lnc2Cancer
hepatocelluar carcinoma qPCR, Western bolt, Luciferase reporter assayRIP etc. liver cancer tissue, cell lines (Panc1, MiaPaCa2, Panc28, L3.6pl etc.) up-regulated N/A We found that the expression levels of HULC were positively correlated with those of HBx in clinical HCC tissues. Moreover, we revealed that HBx up-regulated HULC in human immortalized normal liver L-O2 cells and hepatoma HepG2 cells. Luciferase reporter gene assay and chromatin immunoprecipitation (ChIP) assay showed that HBx activated the HULC promoter via cAMP-responsive element-binding protein. We further demonstrated that HULC promoted cell proliferation by methyl thiazolyl tetrazolium, 5-ethynyl-2'-deoxyuridine, colony formation assay, and tumorigenicity assay. Then, we validated that HULC down-regulated p18, which was involved in the HULC-enhanced cell proliferation in vitro and in vivo. In a word, HULC play function through regulating a tumor suppressor gene p18 located near HULC in the same chromosome. 22685290 Lnc2Cancer
HBV-related liver cirrhosis RT-qPCR, RIP HBV-related liver cirrhosis patients up-regulated expression We confirmed the effects of HULC on Tregs differentiation in HBV-related liver cirrhosis. In addition, it was proved that HULC regulates the function of Tregs through down-regulated the level of p18 directly. 25952928
hepatocelluar carcinoma TaqMan SNP array etc. HCC tissue differential expression mutation We conducted a case-control study and genotyped two SNPs, rs7763881 in HULC and rs619586 in MALAT1 Furthermore, the variant genotypes of rs619586 was associated with decreased HCC risk with a borderline significance. 22493738 LncRNADisease Lnc2Cancer
 


Interaction
Interaction target Level of interaction Type of interaction Description PMID Source
miR-372 RNA-RNA binding Acts as a sponge/target mimic for miR-372 reducing its expression and activity. 21256239 LncRNADisease
miR-372 RNA-DNA regulation highly upregulated in liver cancer (HULC) lncRNA sequesters endogenous miR-372 to modulate its own transcriptional upregulation in HCC. 21802130 LncRNADisease
CLOCK RNA-Protein regulation Our observations showed that HULC was able to heighten the expression levels of CLOCK and its downstream circadian oscillators 25622901
p18 RNA-Protein regulation RIP assay showed that HULC down-regulated the level of p18 directly. 25952928
E2F1 RNA-TF regulation HULC activated the promoter of SPHK1 in hepatoma cells through the transcription factor E2F1. E2F1 was capable of binding to the E2F1 element in the SPHK1 promoter. HULC increased the expression of E2F1 in hepatoma cells and levels of HULC were positively correlated with those of E2F1 in HCC tissues. 26540633
SPHK1 RNA-Protein regulation HULC increased SPHK1 in hepatoma cells. 26540633
miR-107 RNA-RNA regulation HULC sequestered miR-107, which targeted E2F1 mRNA 3'UTR, by complementary base pairing. 26540633
TNF-α RNA-Protein regulation HULC expression was decreased with TNF-α treatment. Restoring HULC expression rescued the apoptosis induced by TNF-α. 26981838
miR-9 RNA-RNA regulation HULC modulated miR-9 expression through association with DNA methyltransferases and suppression of miR-9 expression. 26981838