HULC

Summary

HULC (hepatocellular carcinoma up-regulated long non-coding RNA, HGNC:34232) is a long non-coding RNA gene on chromosome 6p24.3.

This gene produces a long RNA that was discovered as upregulated in hepatocellular carcinoma and is associated with cancer progression. Expression of this transcript is regulated by microRNAs and at the transcriptional level by Sp1 family factors. The transcript may regulate gene expression by functioning as a competing RNA for microRNAs.

Source: NCBI Gene 728655 — RefSeq curated summary.

At a glance

• Gene type: non-coding (lncRNA) — no protein product; not a drug target. Variant/disease associations are omitted (they would be positional, from an overlapping protein-coding gene).

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:34232
Approved symbol	HULC
Name	hepatocellular carcinoma up-regulated long non-coding RNA
Location	6p24.3
Locus type	RNA, long non-coding
Status	Approved
Aliases	NCRNA00078, LINC00078, HCCAT1
Ensembl gene	ENSG00000285219
Ensembl biotype	lncRNA
OMIM	612210
Entrez	728655
RNAcentral	URS00026A1D8A — lncRNA, 434 nt, 1 organism(s)

Gene structure

Transcript identifiers

Ensembl transcripts: 217 — 217 lncRNA

ENST00000429060, ENST00000503668, ENST00000642163, ENST00000642168, ENST00000642340, ENST00000642345, ENST00000642357, ENST00000642458, ENST00000642534, ENST00000642622, ENST00000642665, ENST00000642666, ENST00000642760, ENST00000642798, ENST00000642859, ENST00000642877, ENST00000643036, ENST00000643058, ENST00000643083, ENST00000643126, ENST00000643136, ENST00000643141, ENST00000643201, ENST00000643259, ENST00000643311, ENST00000643404, ENST00000643414, ENST00000643415, ENST00000643431, ENST00000643473, ENST00000643526, ENST00000643545, ENST00000643571, ENST00000643635, ENST00000643761, ENST00000643788, ENST00000643832, ENST00000643889, ENST00000643938, ENST00000643953, ENST00000643985, ENST00000644038, ENST00000644070, ENST00000644111, ENST00000644213, ENST00000644248, ENST00000644363, ENST00000644364, ENST00000644441, ENST00000644605, ENST00000644610, ENST00000644654, ENST00000644778, ENST00000644800, ENST00000644837, ENST00000644892, ENST00000645017, ENST00000645047, ENST00000645087, ENST00000645321, ENST00000645322, ENST00000645344, ENST00000645365, ENST00000645379, ENST00000645464, ENST00000645474, ENST00000645486, ENST00000645611, ENST00000645715, ENST00000645747, ENST00000645750, ENST00000645758, ENST00000645796, ENST00000645808, ENST00000645820, ENST00000645863, ENST00000645925, ENST00000645940, ENST00000645970, ENST00000645976, ENST00000646007, ENST00000646043, ENST00000646073, ENST00000646231, ENST00000646294, ENST00000646295, ENST00000646377, ENST00000646403, ENST00000646406, ENST00000646431, ENST00000646488, ENST00000646490, ENST00000646521, ENST00000646706, ENST00000646718, ENST00000646741, ENST00000646749, ENST00000646758, ENST00000646774, ENST00000646784, ENST00000646792, ENST00000646868, ENST00000646876, ENST00000646981, ENST00000646996, ENST00000647039, ENST00000647052, ENST00000647135, ENST00000647156, ENST00000647175, ENST00000647306, ENST00000647365, ENST00000647466, ENST00000665267, ENST00000665625, ENST00000693633, ENST00000701010, ENST00000701034, ENST00000701300, ENST00000701356, ENST00000701376, ENST00000701974, ENST00000702052, ENST00000702144, ENST00000702170, ENST00000702251, ENST00000702332, ENST00000748945, ENST00000748946, ENST00000748947, ENST00000748948, ENST00000748949, ENST00000748950, ENST00000748951, ENST00000748952, ENST00000748953, ENST00000748954, ENST00000748955, ENST00000748956, ENST00000748957, ENST00000748958, ENST00000748959, ENST00000748960, ENST00000748961, ENST00000748962, ENST00000748963, ENST00000748964, ENST00000748965, ENST00000748966, ENST00000748967, ENST00000748968, ENST00000748969, ENST00000748970, ENST00000748971, ENST00000748972, ENST00000748973, ENST00000748974, ENST00000748975, ENST00000748976, ENST00000748977, ENST00000748978, ENST00000748979, ENST00000748980, ENST00000748981, ENST00000748982, ENST00000748983, ENST00000748984, ENST00000748985, ENST00000748986, ENST00000748987, ENST00000748988, ENST00000748989, ENST00000748990, ENST00000748991, ENST00000748992, ENST00000748993, ENST00000748994, ENST00000748995, ENST00000748996, ENST00000748997, ENST00000748998, ENST00000748999, ENST00000749000, ENST00000749001, ENST00000749002, ENST00000749003, ENST00000749004, ENST00000790758, ENST00000790760, ENST00000790761, ENST00000790762, ENST00000790764, ENST00000790765, ENST00000790766, ENST00000790767, ENST00000790768, ENST00000790769, ENST00000790770, ENST00000790771, ENST00000790772, ENST00000790773, ENST00000790774, ENST00000790775, ENST00000790776, ENST00000790777, ENST00000790778, ENST00000790779, ENST00000790780, ENST00000790781, ENST00000790782, ENST00000790783, ENST00000790784, ENST00000790785, ENST00000790786, ENST00000790787, ENST00000790788, ENST00000790789

RefSeq mRNA: 0 — MANE Select: None

Canonical transcript exons

ENST00000429060 — 3 exons

Exon	Start	End
ENSE00003814577	8785117	8785443
ENSE00003818520	8776036	8776173
ENSE00003830310	8784191	8784337

Expression profiles

Bgee: expression breadth ubiquitous, 162 present calls, max score 93.94.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 4.7111 / max 503.1166, expressed in 1308 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
65719	3.2423	1240
65724	0.8504	29
65720	0.3176	160
65726	0.2422	12
203850	0.0349	10
65728	0.0238	10

Top tissues by expression

241 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right lobe of liver	UBERON:0001114	93.94	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	90.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	82.61	gold quality
left testis	UBERON:0004533	80.70	gold quality
right testis	UBERON:0004534	80.37	gold quality
C1 segment of cervical spinal cord	UBERON:0006469	79.89	gold quality
testis	UBERON:0000473	79.07	gold quality
calcaneal tendon	UBERON:0003701	79.04	gold quality
liver	UBERON:0002107	78.24	gold quality
sural nerve	UBERON:0015488	77.84	gold quality
spinal cord	UBERON:0002240	76.33	gold quality
islet of Langerhans	UBERON:0000006	75.55	gold quality
adenohypophysis	UBERON:0002196	75.41	gold quality
nucleus accumbens	UBERON:0001882	74.91	gold quality
anterior cingulate cortex	UBERON:0009835	74.65	gold quality
cortical plate	UBERON:0005343	74.56	gold quality
prefrontal cortex	UBERON:0000451	74.45	gold quality
Brodmann (1909) area 9	UBERON:0013540	74.26	gold quality
pituitary gland	UBERON:0000007	74.22	gold quality
hypothalamus	UBERON:0001898	73.99	gold quality
putamen	UBERON:0001874	73.98	gold quality
colonic epithelium	UBERON:0000397	73.95	gold quality
cerebellar hemisphere	UBERON:0002245	73.53	gold quality
cerebellar cortex	UBERON:0002129	73.48	gold quality
right frontal lobe	UBERON:0002810	73.47	gold quality
right hemisphere of cerebellum	UBERON:0014890	73.38	gold quality
caudate nucleus	UBERON:0001873	73.07	gold quality
amygdala	UBERON:0001876	72.87	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	72.64	gold quality
right lung	UBERON:0002167	72.51	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.94

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): CREB1

Literature-anchored findings (GeneRIF, showing 40)

• role for HULC in post-transcriptional modulation of gene expression in hepatocellular carcinoma [HULC][AY914050] (PMID:17241883)
• A genetic variant in long non-coding RNA HULC contributes to risk of HBV-related hepatocellular carcinoma in a Chinese population. (PMID:22493738)
• up-regulated HULC promotes proliferation of hepatoma cells through suppressing p18 (PMID:22685290)
• IGF2BP1 acts as an adaptor protein that recruits the CCR4-NOT complex and thereby initiates the degradation of the lncRNA HULC. (PMID:23728852)
• These findings indicate for the first time that the expression of HULC in plasma can be used as a noninvasive promising novel biomarker for the diagnosis and/or prognosis of hepatocellular carcinoma. (PMID:23762823)
• high expression levels of HULC, a cancer-related Long non-coding RNA, correlated clinically with human gastric cancer progression. (PMID:24247585)
• HULC functions as an oncogene in hepatoma cells, acting mechanistically by deregulating lipid metabolism through a signaling pathway involving miR-9, PPARA, and ACSL1. (PMID:25592151)
• POLR2E rs3787016 C/T and HULC rs7763881 were associated with a significantly decreased risk for ESCC 0.005). ANRIL rs2151280 T/C SNP was not associated with risk of ESCC. (PMID:25874495)
• Our results indicated that HULC is a novel molecule involved in osteosarcoma progression (PMID:26045809)
• upregulation of HULC in tumor tissues was positively associated with HCC survival. (PMID:26136615)
• results suggested that miR-203 played tumor suppressive roles by downregulating ADAM9 and HULC and indicated its potential application in cancer treatment (PMID:26179263)
• Sp transcription factors and metformin regulate expression of the long non-coding RNA HULC in hepatocellular carcinoma cell lines. (PMID:26317792)
• CUDR causes highly upregulated in liver cancer, HULC and beta-catenin abnormal expression by inhibiting HULC promoter methylation and promoting beta-catenin promoter-enhancer chromatin looping formation mediated by CUDR-ccctc-binding factor (CTCF) complex. (PMID:26347501)
• Results show circulating HULC and Linc00152 were significantly up-regulated in plasma samples of hepatocellular carcinoma (HCC) patients and suggest they may act as novel biomarkers for HCC. (PMID:26356260)
• Data show that long non-coding RNA HULC promotes tumor angiogenesis in liver cancer through microRNA miR-107/E2F1 transcription factor (E2F1)/sphingosine kinase 1 (SPHK1) signaling. (PMID:26540633)
• High HULC expression is associated with angiogenesis in gliomas. (PMID:26894862)
• Findings demonstrated that during atherosclerosis, HULC plays a significant role in the attenuation of TNF-alpha-induced apoptosis through association with DNA methyltransferases and suppression of miR-9 expression. (PMID:26981838)
• HULC was an key predictive factor for Diffuse large B-cell lymphoma diagnosis and prognosis from sizable samples through the long time follow-ups. (PMID:27044827)
• HULC could be a potential prognostic biomarker in osteosarcoma. (PMID:27253450)
• 200a-3p and ZEB1 may have roles in HULC LncRNA enhancement of epithelial-mesenchymal transition to promote tumorigenesis and metastasis of hepatocellular carcinoma (PMID:27285757)
• HULC is a good predictor of gastric cancer prognosis, and may represent a serum tumor marker for early diagnosis and monitoring progression. (PMID:27322075)
• HULC is up-regulated in human primary colorectal carcinoma tissues. HULC’s oncogenic functions are partially through directly binding with EZH2, and then epigenetically repressing NKD2 expression. (PMID:27496341)
• haploinsufficiency of HULC/MALAT1 plays an important role in malignant growth of liver cancer stem cell. (PMID:27782152)
• H19 and HULC, up-regulated by oxidative stress, regulate CCA cell migration and invasion by targeting IL-6 and CXCR4 via ceRNA patterns of sponging let-7a/let-7b and miR-372/miR-373, respectively. (PMID:27809873)
• HULC acts as an oncogene lncRNA in triple-negative breast cancer (TNBC) and as an independent poor prognostic factor in TNBC patients. (PMID:27986124)
• promotes the phosphorylation of YB-1 through the extracellular signal-regulated kinase pathway, in turn regulates the interaction of YB-1 with certain oncogenic mRNAs, and consequently accelerates the translation of these mRNAs in the process of hepatocarcinogenesis (PMID:28027578)
• HULC promotes cell proliferation by regulating PI3K/AKT signaling pathway in chronic myeloid leukemia. (PMID:28069548)
• This meta-analysis is the first to demonstrate that high expression of the long noncoding RNA HULC is related to poor prognosis for cancer patients. (PMID:28146578)
• data reveals that the pathway ‘HULC/USP22/Sirt1/ protective autophagy’ attenuates the sensitivity of hepatocellular carcinoma cells to chemotherapeutic agents, suggesting that this pathway may be a novel target for developing sensitizing strategy to hepatocellular carcinoma chemotherapy (PMID:28166203)
• These meta-analysis data demonstrate that higher HULC expression can be a useful prognostic biomarker in human cancers (PMID:28199963)
• The results indicate that HULC expression level is an independent prognostic biomarker for unfavorable OS and metastasis in general tumors. (PMID:28315877)
• HULC activates p53-p21 pathway and promotes nasopharyngeal carcinoma cell growth. (PMID:28445086)
• HULC enhanced the level of ubiquitin-specific peptidase 22 (USP22), which decreased ubiquitin-mediated degradation of COX-2 protein by removing the conjugated polyubiquitin chains from COX-2 and finally stabilized COX2 protein. (PMID:28634076)
• Expression levels of HULC are positively correlated with those of HMGA2 in clinical hepatocellular carcinoma tissues. Data suggest that HULC up-regulates expression of HMGA2 in hepatocytes and enhances hepatocarcinogenesis; microRNA-186 inhibits HMGA2 expression by targeting the 3prime-untranslated region of HMGA2 mRNA. (HULC = HULC long non-coding RNA HULC; HMGA2 = high mobility group AT-hook 2) (PMID:28765279)
• High HULC expression is associated with metastasis in cancers. (PMID:29110261)
• meta-analysis of value as prognostic biomarker of survival in cancer (PMID:29145271)
• rs7763881 and serum HULC were associated with colorectal cancer in Egyptian patients. (PMID:29176650)
• This study indicated that metformin imposed inhibitory effect on the HBV-associated HCC by negatively regulating the HULC/p18/miR-200a/ZEB1 signaling pathway. (PMID:29231260)
• The mechanism of low dose irradiation-induced hepatocarcinogenesis through HULC/CDKN1 signaling. (PMID:29573465)
• Data found a promoter rs1041279 SNP was associated with an increased hepatocellular cancer (HCC) risk. A more significant odds ratio value for increased HCC risk was shown in the male subgroup. Furthermore, multi-logistic regression analysis and MDR analysis consistently revealed a three-way interaction model, smoking-drinking-rs2038540 polymorphism, which was suggested to be the best predictive model for HCC. (PMID:29803923)

Cross-species orthologs

0 orthologs

Protein

Non-coding RNA — no protein product; not a drug target.

Function

No curated pathway, Gene-Ontology, or interaction data.

Disease & clinical

No curated disease, variant, or cancer-driver associations.

Drugs & pharmacology

No drug or pharmacology data — not an established drug target.