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Table 1 | HAL-mediated HIF signaling control and cancer progression

From: Signaling in and out: long-noncoding RNAs in tumor hypoxia

lncRNAStatus upon hypoxiaHIF involvementCancer TypesClinical associationFunctional ImpactInteractorTarget/EffectMechanistic ClassificationRefs
Not further induced in nonpapillary disease, but can be induced in lymphocytesN.D.
(2 Putative HREs)
Renal carcinoma• Up-regulated in non-papillary clear-cell renal carcinomaN.D.HIF1A mRNAHIF1A mRNA stabilitymRNA stability control
(Binding of HIF1A-AS2 to the HIF1A mRNA 3′-UTR could possibly expose AU-rich elements and thus increase the degradation of HIF1A mRNA)
[42, 43]
Up-regulatedN.D.Human umbilical vein endothelial cells (HUVECs)• Up-regulated in HUVECs in hypoxiaHUVECs viability ↑
Migration ability ↑
Tube formation ↑
miR-153-3pThe expression of HIF-1αSequestration of miRNAs
(Down-regulation of miR-153-3p-mediated repression of HIF-1α expression)
Up-regulatedN.D.Bladder cancer• Upregulated in bladder cancer after cisplatin treatmentCisplatin resistance ↑N.D.Promoting HMGA1 expressionTranscriptional regulation
(HIF1A-AS2 promoting the expression of HMGA1, which physically interacts with p53, p63, and p73, and therefore inhibits their transcriptional activity on Bax)
Up-regulatedHIF-1α and/or HIF-2α dependent
(2 HREs identified)
Mesenchymal Glioblastoma
Stem-like Cells (M-GSCs)
• Upregulated in M-GSCsGrowth of M-GSCs ↑
Neurosphere-forming capacity of M-GSCs ↑
Glioblastoma tumor growth ↑
IGF2BP2 and DHX9Maintenance of expression of HMGA1Complex scaffold
(The direct interaction among HIF1A-AS2, IGF2BP2 and DHX9 is needed for HMGA1 expression)
[46, 47]
Up-regulatedN.D.Epithelial ovarian cancer (EOC)• Up-regulated in EOCCell apoptosis ↓
Cell proliferation ↑
Tumorigenesis ↑
Tumor growth ↑
N.D.N.D.Unclear mechanism
(May partially through the aHIF-mediated regulation of certain key mitochondrial apoptosis pathway-related genes, including Bcl-2, Bax, Caspase-7, and Caspase-9)
AGAP2-AS1Up-regulatedN.D.Hepatocellular carcinoma (HCC)• Up-regulated in HCC
• Correlated with adverse clinical features and poor prognosis of HCC
Cell proliferation ↑
Migration and invasion ↑
EMT progression ↑
Apoptosis ↓
miR-16-5pThe expression of ANXA11Sequestration of miRNAs
(Down-regulation of miR-16-5p-mediated repression of ANXA11)
ANRIL (CDKN2B-AS1)Up-regulatedHIF-1α dependent
(1 HRE identified)
Osteosarcoma• Up-regulated in osteosarcomaHypoxic viability ↑
Hypoxia-induced Invasion ↑
Hypoxia-induced apoptosis ↓
N.D.N.D.Unclear mechanism
(Possibly through epigenetic modification)
BC005927Up-regulatedHIF-1α dependent
(2 HREs identified)
Gastric cancer (GC)• Up-regulated in GC
• Correlated with higher tumor-node-metastasis stages and poorer prognoses
Metastasis ↑N.D.N.D.Transcriptional regulation
(The neighboring gene, EPHB4, a metastasis-related gene, is regulated by BC005927)
BX111887 (ZEBTR)Up-regulatedHIF-1α dependent
(1 HRE identified)
Pancreatic cancer (PC)• Upregulated in PC
• Correlated with late TNM stage, lymphatic invasion and distant metastasis
Proliferation ↑
Migration ↑
Invasion ↑
YB1ZEB1 promoterTranscriptional regulation
(BX111 promotes ZEB1 transcription by recruiting YB1 to ZEB1 promoter)
CASC9N.D.N.D.Nasopharyngeal carcinoma (NPC)Up-regulated in NPC tissuesGlycolysis and tumorigenesis ↑
Cell growth ↑
HIF-1αThe stability of HIF-1αProtein Stability
(CASC9 interacts with HIF-1α and enhances the stabilization of HIF-1α)
Down-regulatedDownregulated by binding of HIF-1α/HDAC1 complex to CF129 promoterPancreatic cancer (PC)• Down-regulated in PC
• Low CF129 expression predicted short overall survival
Invasion and metastasis ↓p53 and E3 ligase MKRN1FOXC2 transcriptionPost-Translational modification
(CF129 directly binds to p53 and E3 ligase MKRN1, inducing p53 protein ubiquitination and degradation, and thereby suppressing FOXC2 transcription)
(treatment of hypoxia mimetic, CoCl2)
N.D.Colorectal cancerDown-regulated in colorectal cancerEMT and autophagy ↓N.D.N.D.Unclear mechanism
(May partially through suppressing expression levels of HIF-1α, LC3-I, LC3-II, Beclin-1 and EMT associated proteins under hypoxia)
Down-regulatedHIF-1α dependent, HIF-2α independentClear cell renal cell
carcinoma (ccRCC)
• Up-regulated in ccRCC
• Associated with poor overall survival and progression-free survival
Cell migration ↑
Proliferation ↑
N.D.N.D.Unclear mechanism
(May partially through the CRPAT4-mediated regulation of migration-associated gene AVL9 expression)
DANCRN.D.N.D.Nasopharyngeal carcinoma (NPC)• Up-regulated in NPC
• Associated with poor prognosis
Metastasis ↑
Invasion ↑
HIF-1α mRNA stabilitymRNA stability control
(DANCR could increase HIF-1α mRNA stability through interacting with the NF90/NF45 complex)
DARS-AS1Up-regulatedHIF-1α dependent, But HIF-2α independent (2 HREs identified)Myeloma• Up-regulated in myeloma
• Correlated with poor prognosis
Survival ↑
Tumorigenesis ↑
RBM39RBM39 stabilityPost-Translational modification
(The interaction between DARS-AS1 and RNA-binding protein 39 (RBM39) impedes the interaction between RBM39 and its E3 ubiquitin ligase RNF147, preventing RBM39 from degradation)
EIF3J-AS1 (EIF3J-DT)Up-regulatedN.D.Hepatocellular carcinoma (HCC)• Up-regulated in HCC tissues
• Correlated with tumor size, vascular invasion, tumor stage and poor prognosis
Cell proliferation ↑
Migration ↑
Invasion ↑
miR-122-5pThe expression of CTNND2Sequestration of miRNAs
(Down-regulation of miR-122-5p-mediated repression of CTNND2)
ENST00000480739 (RPL13AP23)N.D.N.D.Pancreatic ductal adenocarcinoma
• Down-regulated in PDAC
• Associated with tumor node metastasis (TNM) stage and lymph node metastasis
• Independent risk factor for PDAC survival following surgery
Invasion ↓
OS-9 mRNA & protein ↑
N.D.Transcription of OS-9 (Negative regulation of HIF-1α)Epigenetic and transcriptional regulation
(ENST00000480739 induces OS-9 expression at the transcriptional level, possibly through modifying the H3K27 acetylation level of OS9 gene promoter)
FALECUp-regulatedHIF-1α inducibleProstate cancer (PCa)• Up-regulated in PCa
• Independent prognostic factor
Cell proliferation ↑
Migration and invasion ↑
N.D.N.D.Unclear mechanism
(May partially through the FALEC-mediated regulation of p21 and its downstream components expression)
FAM201AN.D.N.D.Non-small cell lung cancer
• Up-regulated in tissues obtained from NSCLC patients resistant to radiotherapyCell proliferation ↑
Apoptosis (under X-ray irradiation) ↓
miR-370The expression of EGFRSequestration of miRNAs
(Down-regulation of miR-370-mediated repression of EGFR)
FEZF1-AS1N.D.N.D.Pancreatic cancer• Upregulated in pancreatic cancerCell proliferation ↑
Invasion ↑
miR-142 and miR-133aThe expression of HIF-1α and EGFRSequestration of miRNAs
(Down-regulation of miR-142- and miR-133a-mediated repression of HIF-1α and EGFR expression)
GAPLINCUp-regulatedHIF-1α (2 HREs identified)
(2 HREs)
Gastric cancer• Upregulated in GC
• High expression of GAPLINC correlates with poorer survival
• GAPLINC correlates with CD44 activation
Proliferation ↑
Apoptosis ↓
Invasion ↑
Migration ↑
miR-211-3pThe expression of CD44Sequestration of miRNAs
(Down-regulation of miR-211-3p-mediated repression of CD44)
[64, 65]
H19Up-regulatedN.D.Breast cancer stem cells (BCSCs)• H19 expression strongly correlates with PDK1 in primary breast carcinomasGlycolysis ↑
BCSC maintenance ↑
let-7The expression of HIF-1αSequestration of miRNAs
(Down-regulation of let-7-mediated repression of HIF-1α expression)
Up-regulatedN.D.Multiple Myeloma (MM)N.D.The expression of the hypoxia induced genes ↑
Adhesion on stromal cells ↑
N.D.N.D.HIF-1α nuclear translocation
(H19 is required for HIF-1α nuclear translocation and the expression of the hypoxia-induced genes, such as CXCR4 and Snail)
Up-regulatedHIF-1α dependent
(3 HREs identified)
Glioblastoma (GBM)• Up-regulated in GBM
• Correlated with poor prognosis
• The HIF-1α levels were positively correlated with H19 levels in GBM specimens
Migration and invasion ↑
Tumor growth ↑
miR-181dThe expression of β-cateninSequestration of miRNAs
(Down-regulation of miR-181d-mediated repression of β-catenin expression)
Up-regulatedN.D.Prostate Cancer• Upregulated by estrogen or hypoxia
• Reduced upon combined treatment
Cell motility ↓
Invasion ↓
N.D.Repression of beta3 and beta4 IntegrinsUnclear mechanism
(Combined Estrogen and Hypoxia treatment could cause H19 down-regulation, followed by up-regulation of both β3 and β4 Integrins and E-cadherin)
Up-regulatedN.D.Breast cancer, Non-small cell lung carcinoma (NSCLC)• Up-regulated in NSCLC with chronic obstructive pulmonary disease (COPD)
• Up-regulated in all common metastatic sites tested
Migration and invasion ↑
Tumor growth ↑
N.D.Up-regulation of miR-675-5pUnclear mechanism
(H19 could induce upregulation of miR-675-5p, whereas P53 is a target gene of miR-675-5p and P53 downstream target genes involved in EMT, survival and tumorigenesis are thereby repressed)
[73, 74]
HAS2-AS1Up-regulatedHIF-1α dependent (1 HRE identified)Oral squamous cell carcinoma (OSCC)• Up-regulated in OSCCEMT ↑N.D.N.D.Unclear mechanism
(HAS2-AS1-mediated hypoxia-induced EMT is dependent on cell-adhesion molecule CD44 and RHAMM)
HIF2PUTN.D.N.D.Osteosarcoma• Expression of HIF2PUT is correlated with HIF2A mRNACell proliferation and migration ↓
Expression of CSC marker CD133 ↓
Sphere-forming ability ↓
N.D.Transcription of HIF2ATranscriptional regulation
(HIF-2α was positively regulated by lncRNA HIF2PUT)
N.D,N.D.Osteosarcoma cancer stem cell• Down-regulated in osteosarcoma cell lines
• A strong positive correlation between relative HIF2PUT and HIF-2α level in osteosarcoma cancer tissues
Proliferation ↓
Migration and invasion ↓
Sphere-formation ↓
N.D.N.D.Unclear mechanism
(May partly through HIF2PUT-mediated regulation of HIF-2 expression)
HINCUT-1 (uc.475)Up-regulatedHIF-1α dependent
(3 HREs identified)
Colon and breast cancer cell linesN.D.Hypoxic cell proliferation ↑N.D.N.D.Transcriptional regulation
(HINCUT-1 is required for the expression of OGT mRNA expression and global O-GlcNAcylation of proteins)
HOTAIRN.D.N.D.Renal cell carcinoma• Upregulated and correlated with tumor progressionRCC proliferation ↑
Migration and EMT ↑
Apoptosis ↓
miR-217The expression of HIF-1α/AXLSequestration of miRNAs
(Down-regulation of miR-217-mediated repression of HIF-1α/AXL expression)
Up-regulatedHIF-1α dependent
(1 HRE identified)
Non-small cell lung carcinoma (NSCLC)• High level of HOTAIR is associated with poor clinical outcome in multiple cancersCell proliferation under hypoxia ↑
Invasion & migration under hypoxia ↑
Apoptosis under hypoxia ↓
N.D.N.D.Unclear mechanism
(Possibly through HOTAOR-mediated epigenetic modification)
[80, 81]
HOTTIPUp-regulatedHIF-1α dependentGlioma• Up-regulated in glioma
• Associated with metastasis and poor patient survival
Invasion ↑
Migration ↑
miR-101The expression of ZEB1Sequestration of miRNAs
(Down-regulation of miR-101-mediated repression of ZEB1)
(c-Myc-mediated repression)
Multiple cell lines (HeLa, HCT116, H1299, P493 and 293 T)N.D.Glycolysis ↓IDH1IDH1 dimerizationProtein Dimerization
(IDH1-AS1 interacts with IDH1 and promotes Its Homo-dimerization)
LINC01436Up-regulatedN.D.Non-small cell lung cancer
• Up-regulated in NSCLC
• Associated with poor overall survival
Cell growth ↑
Migration and invasion ↑
miR-30a-3pThe expression of EPAS1Sequestration of miRNAs
(Down-regulation of miR-30a-3p-mediated repression of EPAS1)
lincRNA-p21 (TP53COR1)Up-regulatedHIF-1α dependent & preference
(2 HREs identified)
Cervical, lung and breast cancer cell linesN.D.Hypoxic glycolysis ↑
Tumor growth ↑
HIF-1α and VHLThe disruption of the VHL-HIF-1α interactionProtein-Protein Interaction Decoy
(Stabilization of HIF-1α by disrupting the VHL-HIF-1α Interaction)
Up-regulatedN.D.Hepatoma, gliomaN.D.Apoptosis ↓
Cell proliferation and motility ↑
Autophagy ↑
N.D.N.D.Unclear mechanism
(LincRNA-p21 could promote autophagy of hypoxic tumor cells by up-regulating HIF-1α protein levels and suppressing Akt/mTOR/P70S6K signaling pathways)
linc-RORUp-regulatedN.D.Hepatocellular cancerUp-regulated in malignant liver cancer cellsCell viability during hypoxia ↑
Tumor growth ↑
miR-145The expression of p70S6K1 (RPS6KB1)Sequestration of miRNAs
(Down-regulation of miR145-mediated repression of p70S6K1 expression)
N.D.N.D.Triple-negative breast cancer• Upregulated in TNBC
• High levels of LINK-A correlated with unfavorable recurrence-free survival for breast cancer patients
Glycolysis ↑
Tumor growth ↑
BRK and LRRK2 kinaseHIF-1α phosphorylationComplex scaffold
(LINK-A facilitates the recruitment of BRK and LRRK2 kinase activation, thereby causing HIF-1α stabilization, HIF-1α/p300 interaction, and activation of HIF-1α transcriptional programs under normoxic conditions)
LncHIFCAR (MIR31HG)Up-regulatedHIF-1α dependentOral cancer• Up-regulated in oral cancer
• High levels of LncHIFCAR predicted worse overall survival and recurrence-free survival
Hypoxic glycolysis ↑
Tumor metastasis ↑
Invasion and migration ↑
Hypoxic cell proliferation ↑
Sphere-forming ability ↑
HIF-1αActivation of HIF-1 signalingTranscriptional regulation
(LncHIFCAR acts as HIF-1α coactivator)
lncRNA-AK058003Up-regulatedN.D.Gastric cancerUp-regulated in GCInvasion & migration ↑
Metastasis ↑
N.D.N.D.Epigenetic regulation
(AK058003 expression is positively correlated with SNCG expression and SNCG promoter demethylation)
lncRNA-EFNA3Up-regulatedHIF-1α dependent
(1 HRE identified)
Breast cancerA strong correlation between high EFNA3 expression and shorter metastasis-free survival in breast cancer patientsCell extravasation ↑
Metastatic dissemination ↑
miR-210The expression of EFNA3Sequestration of miRNAs
(Down-regulation of miR-210-mediated repression of EFNA3)
Up-regulatedHIF-1α dependent
(3 putative HREs found)
Breast cancerUp-regulated in triple negative breast cancerMigration ↑
Cancer stem cell phenotype ↑
Mammospheres ↑
Clonogenic growth ↑
Histones and hnRNPs.N.D.Unclear mechanism
(The binding of lncRNA-HAL to histones and hnRNPs may suggest a participation at the chromatin level and transcriptional regulation)
lncRNA-LET (NPTN-IT1)Down-regulatedHIF-1α dependent
(Indirect: Histone deacetylation)
Lung squamous-cell cancer (LSCC), hepatocellular carcinoma (HCC) and colorectal cancer (CRC)• Down-regulated in in LSCC, HCC and CRC
• Correlated with hypoxia, histone acetylation disorder and metastasis in HCC
Metastasis ↓
Invasion ↓
NF90 (RNA-binding protein)HIF1A mRNA stabilitymRNA stability control
(The association between lncRNA-LET and NF90 protein enhanced the degradation of NF90, thereby decreasing HIF1A mRNA)
VHL-dependentHIF-2α dependent
(1 HRE identified)
Renal cell carcinomaDifferentially regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner in RCC clinical specimensHypoxic cell cycle progression (VHL-restored RCC cells) ↑
Hypoxic cell cycle progression (VHL-mutant RCC cells) ↓
AR (androgen receptor)AR ubiquitination and degradationPost-Translational modification
(lncRNA-SARCC could promote AR degradation via ubiquitin-mediated proteolysis to suppress AR/HIF-2α/C-MYC signals)
lncTCF7 (WSPAR)Up-regulatedN.D.Glioma• Up-regulated in glioma
• Associated with WHO grade and tumor size
Cell migration ↑
Proliferation ↑
Tumorigenicity ↑
N.D.N.D.Unclear mechanism
(LncTCF7 could promote the migration and proliferation of glioma cell partially through activating the Wnt signalling pathway)
MALAT1Up-regulatedHIF-2α dependent & preference
Hepatocellular carcinomaN.D.Cell growth ↑
Glycolysis ↑
Migration & invasion ↑
Vasculature formation ↑
Metastasis ↑
N.D.N.D.Post-Translational modification
(MALAT1 decreases hydroxylation of HIF-1α/HIF-2α, possibly through disassociation of the VHL protein from HIF-1α/HIF-2α)
[96, 97]
Up-regulatedN.D.Lung adenocarcinomaN.D.Proliferation ↑
Migration ↑
Invasion ↑
PTB-associated splicing factor (PSF)GAGE6 promoterTranscriptional regulation
(The physical interaction of MALAT1 and PSF released the binding of PSF to GAGE6 promoter)
[98, 99]
Up-regulatedN.D.Hepatocellular carcinomaN.D.Proliferation ↑
Migration and invasion ↑
Apoptosis ↓
miR-200aN.D.Sequestration of miRNAs
(Down-regulation of miR-200a)
MEG3Up-regulatedN.D.PheochromocytomaN.D.Hypoxia-induced PC12 cell injury ↑Methylation proteins (DNMT3a, DNMT3b, and MBD1)TIMP2 promoter methylationEpigenetic regulation
(MEG3 recruited methylation proteins DNMT3a, DNMT3b, and MBD1 and accelerated TIMP2 promoter methylation, which in turn inhibited its expression)
MTA2TRUp-regulatedHIF-1α dependent
(1 HRE identified)
Pancreatic cancer (PC)Upregulated in PC tissuesCell proliferation ↑
Invasion ↑
Activating transcription factor 3 (ATF3)The expression of MTA2
(MTA2 stabilizes the HIF-1α via deacetylation)
Transcriptional regulation
(MTA2TR transcriptionally upregulates MTA2 expression by recruiting ATF3 to the promoter area of MTA2)
NEAT1Up-regulatedHIF-2α dependentNon-small cell lung cancer (NSCLC)• Up-regulated in NSCLC
• Associated with TNM stage and metastasis
Cell proliferation ↑
Migration and invasion ↑
miR-101-3pSOX9/Wnt/β-catenin signaling pathwaySequestration of miRNAs
(Down-regulation of miR-101-3p-mediated repression of SOX9/Wnt/β-catenin signaling pathway)
Up-regulatedHIF-2α dependent & preferenceBreast cancerHigh expression of NEAT1 is associated with poor survival of breast cancer patientsProliferation ↑
Apoptosis ↓
Clonogenic survival ↑
Paraspeckle formation ↑
N.D.N.D.Complex scaffold
(Induces paraspeckle formation, thereby enhancing cancer cell survival in hypoxia)
[12, 104,105,106]
Up-regulatedN.D.Breast cancer• N.D.N.D.NDRG1NDRG1 degradationPost-Translational modification
(NDRG-OT1 could promote NDRG1 degradation via ubiquitin-mediated proteolysis)
NORADUp-regulatedN.D.Pancreatic cancer (PC)• Upregulated in PC
• Correlated with shorter overall survival
Migration ↑
Invasion ↑
Metastasis ↑
miR-125a-3pThe expression of RhoASequestration of miRNAs
(Down-regulation of miR-125a-3p-mediated repression of RhoA)
Up-regulatedHIF-1α dependent
(1 HRE identified)
Pancreatic cancer• Upregulated in pancreatic cancer
• A positive correlation between NUTF2P3 and KRAS
• Associated with tumor stage and prognosis
Cell viability, proliferation ↑
Invasion ↑
KRAS expression ↑
Metastasis ↑
miR-3923The expression of KRASSequestration of miRNAs
(Down-regulation of miR-3923-mediated repression of KRAS)
PCGEM1Up-regulatedN.D.Gastric cancer (GC)Up-regulated in GCInvasion and metastasis ↑N.D.N.D.Unclear mechanism
(Partially through regulating SNAI1, a key transcription factor of EMT)
PVT1N.D.N.D.Nasopharyngeal carcinoma (NPC)• Up-regulated in NPC
• Up-regulation is associated with a poor prognosis in NPC patients
NPC cell proliferation ↑
Colony formation ↑
In vivo tumorigenesis ↑
KAT2A (chromatin modification factor)Transcription of NF90 (RNA-binding protein)Epigenetic regulation
(PVT1 serves as a scaffold for KAT2A, which mediates H3K9 acetylation, recruiting the nuclear receptor binding protein TIF1β to activate NF90 transcription, thereby increasing HIF-1α mRNA stability)
N.D.N.D.Hepatocellular carcinoma (HCC)Up-regulated in HCC tissues and cell linesCell proliferation ↑
Migration ↑
Invasion and iron uptake ↑
Apoptosis ↓
miR-150The expression of HIG2 (Hypoxia-inducible protein 2)Sequestration of miRNAs
(Down-regulation of miR-150-mediated repression of HIG2)
N.D.N.D.Gastric cancer• Upregulated in GC tissues and cell lines
• High expression levels correlated with advanced tumor stage and lymph node metastasis
GC cell proliferation ↑
GC cell invasion ↑
miR-186The expression of HIF-1αSequestration of miRNAs
(Down-regulation of miR-186-mediated repression of HIF-1α expression)
Up-regulatedN.D.Non-small cell lung cancer (NSCLC)• Up-regulated in HIF-1α high group compared with HIF-1α low group
• Negatively correlated with miR-199a-5p expression in NSCLC tissues
Cell proliferation ↑miR-199a-5pThe expression of HIF-1αSequestration of miRNAs
(Down-regulation of miR-199a-5p-mediated repression of HIF-1α expression)
treatment of hypoxia mimetic CoCl2)
N.D.Cervical Cancer• Up-regulated in Cervical cancer
• Correlates with poorer overall survival
Cell proliferation ↑
Migration and invasion ↑
Apoptosis ↓
Cisplatin resistance ↑
N.D.N.D.Unclear mechanism
(Possible involvement of the interaction with nucleolin)
N.D.N.D.Hepatocellular carcinoma
The expression levels of RERT-lncRNA and EGLN2 were significantly correlated in HCCEGLN2 expression ↑N.D.N.D.Transcriptional regulation
(RERT-lncRNA induces EGLN2/PHD1 expression at the transcriptional level)
UBE2CP3N.D.N.D.Hepatocellular carcinoma (HCC)• Up-regulated in HCC, especially in high EV (endothelial vessel) density tissues
• UBE2CP3 expression combined with EV density is associated with HCC patient prognosis
Proliferation ↑
Migration ↑
Tube formation ↑
N.D.N.D.Unclear mechanism
(May partially through UBE2CP3-induced increase in the secretion of VEGFA into the supernatant via activation of the ERK/HIF-1α signaling pathway)
UCA1Up-regulatedHIF-1α-dependentEstrogen receptor (ER)-positive breast cancerN.D.Tamoxifen resistance ↑miR-18aThe expression of HIF-1αSequestration of miRNAs
(Down-regulation of miR-18a-mediated repression of HIF-1α expression)
Up-regulatedN.D.Hypoxia-resistant gastric cancer (HRGC)Upregulated in HRGC cellsMigration ↑miR-7-5pThe expression of EGFRSequestration of miRNAs
(Down-regulation of miR-7-5p-mediated repression of EGFR)
Up-regulatedN.D.Acute myeloid leukemia (AML)Upregulated following ADR (adriamycin)-based chemotherapyCytotoxic effect of ADR ↓
HIF-1α-dependent glycolysis ↑
miR-125aThe expression of HK2Sequestration of miRNAs
(Down-regulation of miR-125a-mediated repression of HK2)
Up-regulatedHIF-1α dependent
(2 HREs)
Bladder cancer• Upregulated in bladder cancer
UCA1 expression associated with the clinical stage and histologic grade of bladder cancer
Cell proliferation under hypoxia ↑
Invasion & migration under hypoxia ↑
Apoptosis under hypoxia ↓
N.D.N.D.Unclear mechanism
(UCA1 could modulate the expression of several genes involved in tumorigenic potential, drug resistance and embryonic development)
[121, 122]
Up-regulatedHIF-1α dependent
(1 HRE identified)
OsteosarcomaN.D.Cell growth ↑N.D.N.D.Unclear mechanism
(May partially through inactivating the PTEN/AKT signaling pathway)
WT1-ASUp-regulatedHIF-1 dependent
(DNA demethylation of the CpG island)
Myeloid Leukemia• Upregulated in Wilms’ tumors
• Aberrant WT1-AS splicing often found in acute myeloid leukemia
N.D.N.D.N.D.Epigenetic regulation
(WT1-AS mediates hypoxia-induced WT-1 mRNA upregulation through modulating histone methylation)
[124, 125]
ZEB2-AS1Up-regulatedHIF-1α dependentGastric cancer
• Upregulated in GC
• Correlated with poor differentiation, lymph node metastasis and distant metastasis
Cell proliferation and growth ↑
Invasion ↑
In vivo tumor growth ↑
miR-143-5pThe expression of HIF-1αSequestration of miRNAs
(Down-regulation of miR-143-5p-mediated repression of HIF-1α expression)
  1. Abbreviation: CRC colorectal cancer, CSC cancer stem cell, EMT epithelial–mesenchymal transition, GC Gastric cancer, HCC hepatocellular cancer, HRE hypoxia response element, HUVECs human umbilical vein endothelial cells, ICC Immunocytochemistry, LC lung cancer, M-GSCs Mesenchymal glioblastoma multiforme stem-like cells, N.D. Not determined, NSCLC non-small cell lung carcinoma, OSCC Oral squamous cell carcinoma, PDAC pancreatic ductal adenocarcinoma, RCC Renal Cell Carcinoma, RNP ribonucleic protein, TNM tumor, node, metastasis, VHL von Hippel-Lindau protein, WHO World Health Organization