Table 1 | HAL-mediated HIF signaling control and cancer progression
From: Signaling in and out: long-noncoding RNAs in tumor hypoxia
lncRNA | Status upon hypoxia | HIF involvement | Cancer Types | Clinical association | Functional Impact | Interactor | Target/Effect | Mechanistic Classification | Refs |
|---|---|---|---|---|---|---|---|---|---|
aHIF (HIF1A-AS2) | Not further induced in nonpapillary disease, but can be induced in lymphocytes | N.D. (2 Putative HREs) | Renal carcinoma | • Up-regulated in non-papillary clear-cell renal carcinoma | N.D. | HIF1A mRNA | HIF1A mRNA stability | mRNA 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) | |
Up-regulated | N.D. | Human umbilical vein endothelial cells (HUVECs) | • Up-regulated in HUVECs in hypoxia | HUVECs viability ↑ Migration ability ↑ Tube formation ↑ | miR-153-3p | The expression of HIF-1α | Sequestration of miRNAs (Down-regulation of miR-153-3p-mediated repression of HIF-1α expression) | [44] | |
Up-regulated | N.D. | Bladder cancer | • Upregulated in bladder cancer after cisplatin treatment | Cisplatin resistance ↑ | N.D. | Promoting HMGA1 expression | Transcriptional regulation (HIF1A-AS2 promoting the expression of HMGA1, which physically interacts with p53, p63, and p73, and therefore inhibits their transcriptional activity on Bax) | [45] | |
Up-regulated | HIF-1α and/or HIF-2α dependent (2 HREs identified) | Mesenchymal Glioblastoma Stem-like Cells (M-GSCs) | • Upregulated in M-GSCs | Growth of M-GSCs ↑ Neurosphere-forming capacity of M-GSCs ↑ Glioblastoma tumor growth ↑ | IGF2BP2 and DHX9 | Maintenance of expression of HMGA1 | Complex scaffold (The direct interaction among HIF1A-AS2, IGF2BP2 and DHX9 is needed for HMGA1 expression) | ||
Up-regulated | N.D. | Epithelial ovarian cancer (EOC) | • Up-regulated in EOC | Cell 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) | [48] | |
AGAP2-AS1 | Up-regulated | N.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-16-5p | The expression of ANXA11 | Sequestration of miRNAs (Down-regulation of miR-16-5p-mediated repression of ANXA11) | [49] |
ANRIL (CDKN2B-AS1) | Up-regulated | HIF-1α dependent (1 HRE identified) | Osteosarcoma | • Up-regulated in osteosarcoma | Hypoxic viability ↑ Hypoxia-induced Invasion ↑ Hypoxia-induced apoptosis ↓ | N.D. | N.D. | Unclear mechanism (Possibly through epigenetic modification) | [50] |
BC005927 | Up-regulated | HIF-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) | [51] |
BX111887 (ZEBTR) | Up-regulated | HIF-1α dependent (1 HRE identified) | Pancreatic cancer (PC) | • Upregulated in PC • Correlated with late TNM stage, lymphatic invasion and distant metastasis | Proliferation ↑ Migration ↑ Invasion ↑ | YB1 | ZEB1 promoter | Transcriptional regulation (BX111 promotes ZEB1 transcription by recruiting YB1 to ZEB1 promoter) | [52] |
CASC9 | N.D. | N.D. | Nasopharyngeal carcinoma (NPC) | Up-regulated in NPC tissues | Glycolysis and tumorigenesis ↑ Cell growth ↑ | HIF-1α | The stability of HIF-1α | Protein Stability (CASC9 interacts with HIF-1α and enhances the stabilization of HIF-1α) | [53] |
CF129 (lncRNA-CF129145.1) | Down-regulated | Downregulated by binding of HIF-1α/HDAC1 complex to CF129 promoter | Pancreatic cancer (PC) | • Down-regulated in PC • Low CF129 expression predicted short overall survival | Invasion and metastasis ↓ | p53 and E3 ligase MKRN1 | FOXC2 transcription | Post-Translational modification (CF129 directly binds to p53 and E3 ligase MKRN1, inducing p53 protein ubiquitination and degradation, and thereby suppressing FOXC2 transcription) | [54] |
CPS1-IT1 | Down-regulated (treatment of hypoxia mimetic, CoCl2) | N.D. | Colorectal cancer | Down-regulated in colorectal cancer | EMT 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) | [55] |
CRPAT4 (RP11-225B17) | Down-regulated | HIF-1α dependent, HIF-2α independent | Clear 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) | [56] |
DANCR | N.D. | N.D. | Nasopharyngeal carcinoma (NPC) | • Up-regulated in NPC • Associated with poor prognosis | Metastasis ↑ Invasion ↑ | NF90/NF45 complex | HIF-1α mRNA stability | mRNA stability control (DANCR could increase HIF-1α mRNA stability through interacting with the NF90/NF45 complex) | [57] |
DARS-AS1 | Up-regulated | HIF-1α dependent, But HIF-2α independent (2 HREs identified) | Myeloma | • Up-regulated in myeloma • Correlated with poor prognosis | Survival ↑ Tumorigenesis ↑ | RBM39 | RBM39 stability | Post-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) | [58] |
EIF3J-AS1 (EIF3J-DT) | Up-regulated | N.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-122-5p | The expression of CTNND2 | Sequestration of miRNAs (Down-regulation of miR-122-5p-mediated repression of CTNND2) | [59] |
ENST00000480739 (RPL13AP23) | N.D. | N.D. | Pancreatic ductal adenocarcinoma (PDAC) | • 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) | [60] |
FALEC | Up-regulated | HIF-1α inducible | Prostate 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) | [61] |
FAM201A | N.D. | N.D. | Non-small cell lung cancer (NSCLC) | • Up-regulated in tissues obtained from NSCLC patients resistant to radiotherapy | Cell proliferation ↑ Apoptosis (under X-ray irradiation) ↓ | miR-370 | The expression of EGFR | Sequestration of miRNAs (Down-regulation of miR-370-mediated repression of EGFR) | [62] |
FEZF1-AS1 | N.D. | N.D. | Pancreatic cancer | • Upregulated in pancreatic cancer | Cell proliferation ↑ Invasion ↑ | miR-142 and miR-133a | The expression of HIF-1α and EGFR | Sequestration of miRNAs (Down-regulation of miR-142- and miR-133a-mediated repression of HIF-1α and EGFR expression) | [63] |
GAPLINC | Up-regulated | HIF-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-211-3p | The expression of CD44 | Sequestration of miRNAs (Down-regulation of miR-211-3p-mediated repression of CD44) | |
H19 | Up-regulated | N.D. | Breast cancer stem cells (BCSCs) | • H19 expression strongly correlates with PDK1 in primary breast carcinomas | Glycolysis ↑ BCSC maintenance ↑ | let-7 | The expression of HIF-1α | Sequestration of miRNAs (Down-regulation of let-7-mediated repression of HIF-1α expression) | [66] |
Up-regulated | N.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) | [67] | |
Up-regulated | HIF-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 ↑ EMT ↑ | miR-181d | The expression of β-catenin | Sequestration of miRNAs (Down-regulation of miR-181d-mediated repression of β-catenin expression) | ||
Up-regulated | N.D. | Prostate Cancer | • Upregulated by estrogen or hypoxia • Reduced upon combined treatment | Cell motility ↓ Invasion ↓ | N.D. | Repression of beta3 and beta4 Integrins | Unclear mechanism (Combined Estrogen and Hypoxia treatment could cause H19 down-regulation, followed by up-regulation of both β3 and β4 Integrins and E-cadherin) | [72] | |
Up-regulated | N.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 ↑ EMT ↑ | N.D. | Up-regulation of miR-675-5p | Unclear 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) | ||
HAS2-AS1 | Up-regulated | HIF-1α dependent (1 HRE identified) | Oral squamous cell carcinoma (OSCC) | • Up-regulated in OSCC | EMT ↑ | N.D. | N.D. | Unclear mechanism (HAS2-AS1-mediated hypoxia-induced EMT is dependent on cell-adhesion molecule CD44 and RHAMM) | [75] |
HIF2PUT | N.D. | N.D. | Osteosarcoma | • Expression of HIF2PUT is correlated with HIF2A mRNA | Cell proliferation and migration ↓ Expression of CSC marker CD133 ↓ Sphere-forming ability ↓ | N.D. | Transcription of HIF2A | Transcriptional regulation (HIF-2α was positively regulated by lncRNA HIF2PUT) | [76] |
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) | [77] | |
HINCUT-1 (uc.475) | Up-regulated | HIF-1α dependent (3 HREs identified) | Colon and breast cancer cell lines | N.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) | [78] |
HOTAIR | N.D. | N.D. | Renal cell carcinoma | • Upregulated and correlated with tumor progression | RCC proliferation ↑ Migration and EMT ↑ Apoptosis ↓ | miR-217 | The expression of HIF-1α/AXL | Sequestration of miRNAs (Down-regulation of miR-217-mediated repression of HIF-1α/AXL expression) | [79] |
Up-regulated | HIF-1α dependent (1 HRE identified) | Non-small cell lung carcinoma (NSCLC) | • High level of HOTAIR is associated with poor clinical outcome in multiple cancers | Cell proliferation under hypoxia ↑ Invasion & migration under hypoxia ↑ Apoptosis under hypoxia ↓ | N.D. | N.D. | Unclear mechanism (Possibly through HOTAOR-mediated epigenetic modification) | ||
HOTTIP | Up-regulated | HIF-1α dependent | Glioma | • Up-regulated in glioma • Associated with metastasis and poor patient survival | EMT ↑ Invasion ↑ Migration ↑ | miR-101 | The expression of ZEB1 | Sequestration of miRNAs (Down-regulation of miR-101-mediated repression of ZEB1) | [82] |
IDH1-AS1 | N.D. | N.D. (c-Myc-mediated repression) | Multiple cell lines (HeLa, HCT116, H1299, P493 and 293 T) | N.D. | Glycolysis ↓ | IDH1 | IDH1 dimerization | Protein Dimerization (IDH1-AS1 interacts with IDH1 and promotes Its Homo-dimerization) | [83] |
LINC01436 | Up-regulated | N.D. | Non-small cell lung cancer (NSCLC) | • Up-regulated in NSCLC • Associated with poor overall survival | Cell growth ↑ Migration and invasion ↑ | miR-30a-3p | The expression of EPAS1 | Sequestration of miRNAs (Down-regulation of miR-30a-3p-mediated repression of EPAS1) | [84] |
lincRNA-p21 (TP53COR1) | Up-regulated | HIF-1α dependent & preference (2 HREs identified) | Cervical, lung and breast cancer cell lines | N.D. | Hypoxic glycolysis ↑ Tumor growth ↑ | HIF-1α and VHL | The disruption of the VHL-HIF-1α interaction | Protein-Protein Interaction Decoy (Stabilization of HIF-1α by disrupting the VHL-HIF-1α Interaction) | [85] |
Up-regulated | N.D. | Hepatoma, glioma | N.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) | [86] | |
linc-ROR | Up-regulated | N.D. | Hepatocellular cancer | Up-regulated in malignant liver cancer cells | Cell viability during hypoxia ↑ Tumor growth ↑ | miR-145 | The expression of p70S6K1 (RPS6KB1) | Sequestration of miRNAs (Down-regulation of miR145-mediated repression of p70S6K1 expression) | [87] |
LINK-A (LINC01139) | 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 kinase | HIF-1α phosphorylation | Complex 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) | [88] |
LncHIFCAR (MIR31HG) | Up-regulated | HIF-1α dependent | Oral 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-1α | Activation of HIF-1 signaling | Transcriptional regulation (LncHIFCAR acts as HIF-1α coactivator) | [89] |
lncRNA-AK058003 | Up-regulated | N.D. | Gastric cancer | Up-regulated in GC | Invasion & migration ↑ Metastasis ↑ | N.D. | N.D. | Epigenetic regulation (AK058003 expression is positively correlated with SNCG expression and SNCG promoter demethylation) | [90] |
lncRNA-EFNA3 | Up-regulated | HIF-1α dependent (1 HRE identified) | Breast cancer | A strong correlation between high EFNA3 expression and shorter metastasis-free survival in breast cancer patients | Cell extravasation ↑ Metastatic dissemination ↑ | miR-210 | The expression of EFNA3 | Sequestration of miRNAs (Down-regulation of miR-210-mediated repression of EFNA3) | [91] |
lncRNA-HAL (lnc-METTL16-2) | Up-regulated | HIF-1α dependent (3 putative HREs found) | Breast cancer | Up-regulated in triple negative breast cancer | Migration ↑ 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) | [92] |
lncRNA-LET (NPTN-IT1) | Down-regulated | HIF-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 stability | mRNA stability control (The association between lncRNA-LET and NF90 protein enhanced the degradation of NF90, thereby decreasing HIF1A mRNA) | [93] |
lncRNA-SARCC (lnc-P2RY1-1) | VHL-dependent | HIF-2α dependent (1 HRE identified) | Renal cell carcinoma | Differentially regulated by hypoxia in a von Hippel-Lindau (VHL)-dependent manner in RCC clinical specimens | Hypoxic cell cycle progression (VHL-restored RCC cells) ↑ Hypoxic cell cycle progression (VHL-mutant RCC cells) ↓ | AR (androgen receptor) | AR ubiquitination and degradation | Post-Translational modification (lncRNA-SARCC could promote AR degradation via ubiquitin-mediated proteolysis to suppress AR/HIF-2α/C-MYC signals) | [94] |
lncTCF7 (WSPAR) | Up-regulated | N.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) | [95] |
MALAT1 | Up-regulated | HIF-2α dependent & preference (1HRE) | Hepatocellular carcinoma | N.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) | |
Up-regulated | N.D. | Lung adenocarcinoma | N.D. | Proliferation ↑ Migration ↑ Invasion ↑ | PTB-associated splicing factor (PSF) | GAGE6 promoter | Transcriptional regulation (The physical interaction of MALAT1 and PSF released the binding of PSF to GAGE6 promoter) | ||
Up-regulated | N.D. | Hepatocellular carcinoma | N.D. | Proliferation ↑ Migration and invasion ↑ Apoptosis ↓ | miR-200a | N.D. | Sequestration of miRNAs (Down-regulation of miR-200a) | [100] | |
MEG3 | Up-regulated | N.D. | Pheochromocytoma | N.D. | Hypoxia-induced PC12 cell injury ↑ | Methylation proteins (DNMT3a, DNMT3b, and MBD1) | TIMP2 promoter methylation | Epigenetic regulation (MEG3 recruited methylation proteins DNMT3a, DNMT3b, and MBD1 and accelerated TIMP2 promoter methylation, which in turn inhibited its expression) | [101] |
MTA2TR | Up-regulated | HIF-1α dependent (1 HRE identified) | Pancreatic cancer (PC) | Upregulated in PC tissues | Cell 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) | [102] |
NEAT1 | Up-regulated | HIF-2α dependent | Non-small cell lung cancer (NSCLC) | • Up-regulated in NSCLC • Associated with TNM stage and metastasis | Cell proliferation ↑ Migration and invasion ↑ | miR-101-3p | SOX9/Wnt/β-catenin signaling pathway | Sequestration of miRNAs (Down-regulation of miR-101-3p-mediated repression of SOX9/Wnt/β-catenin signaling pathway) | [103] |
Up-regulated | HIF-2α dependent & preference | Breast cancer | High expression of NEAT1 is associated with poor survival of breast cancer patients | Proliferation ↑ Apoptosis ↓ Clonogenic survival ↑ Paraspeckle formation ↑ | N.D. | N.D. | Complex scaffold (Induces paraspeckle formation, thereby enhancing cancer cell survival in hypoxia) | ||
NDRG-OT1 (lnc-NDRG1-1) | Up-regulated | N.D. | Breast cancer | • N.D. | N.D. | NDRG1 | NDRG1 degradation | Post-Translational modification (NDRG-OT1 could promote NDRG1 degradation via ubiquitin-mediated proteolysis) | [107] |
NORAD | Up-regulated | N.D. | Pancreatic cancer (PC) | • Upregulated in PC • Correlated with shorter overall survival | Migration ↑ Invasion ↑ EMT ↑ Metastasis ↑ | miR-125a-3p | The expression of RhoA | Sequestration of miRNAs (Down-regulation of miR-125a-3p-mediated repression of RhoA) | [108] |
NUTF2P3-001 (NUTF2P3) | Up-regulated | HIF-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-3923 | The expression of KRAS | Sequestration of miRNAs (Down-regulation of miR-3923-mediated repression of KRAS) | [109] |
PCGEM1 | Up-regulated | N.D. | Gastric cancer (GC) | Up-regulated in GC | Invasion and metastasis ↑ | N.D. | N.D. | Unclear mechanism (Partially through regulating SNAI1, a key transcription factor of EMT) | [110] |
PVT1 | N.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) | [111] |
N.D. | N.D. | Hepatocellular carcinoma (HCC) | Up-regulated in HCC tissues and cell lines | Cell proliferation ↑ Migration ↑ Invasion and iron uptake ↑ Apoptosis ↓ | miR-150 | The expression of HIG2 (Hypoxia-inducible protein 2) | Sequestration of miRNAs (Down-regulation of miR-150-mediated repression of HIG2) | [112] | |
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-186 | The expression of HIF-1α | Sequestration of miRNAs (Down-regulation of miR-186-mediated repression of HIF-1α expression) | [113] | |
Up-regulated | N.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-5p | The expression of HIF-1α | Sequestration of miRNAs (Down-regulation of miR-199a-5p-mediated repression of HIF-1α expression) | [114] | |
Up-regulated 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) | [115] | |
RERT-lncRNA (RAB4B-EGLN2) | N.D. | N.D. | Hepatocellular carcinoma (HCC) | The expression levels of RERT-lncRNA and EGLN2 were significantly correlated in HCC | EGLN2 expression ↑ | N.D. | N.D. | Transcriptional regulation (RERT-lncRNA induces EGLN2/PHD1 expression at the transcriptional level) | [116] |
UBE2CP3 | N.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) | [117] |
UCA1 | Up-regulated | HIF-1α-dependent | Estrogen receptor (ER)-positive breast cancer | N.D. | Tamoxifen resistance ↑ | miR-18a | The expression of HIF-1α | Sequestration of miRNAs (Down-regulation of miR-18a-mediated repression of HIF-1α expression) | [118] |
Up-regulated | N.D. | Hypoxia-resistant gastric cancer (HRGC) | Upregulated in HRGC cells | Migration ↑ | miR-7-5p | The expression of EGFR | Sequestration of miRNAs (Down-regulation of miR-7-5p-mediated repression of EGFR) | [119] | |
Up-regulated | N.D. | Acute myeloid leukemia (AML) | Upregulated following ADR (adriamycin)-based chemotherapy | Cytotoxic effect of ADR ↓ HIF-1α-dependent glycolysis ↑ | miR-125a | The expression of HK2 | Sequestration of miRNAs (Down-regulation of miR-125a-mediated repression of HK2) | [120] | |
Up-regulated | HIF-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) | ||
Up-regulated | HIF-1α dependent (1 HRE identified) | Osteosarcoma | N.D. | Cell growth ↑ | N.D. | N.D. | Unclear mechanism (May partially through inactivating the PTEN/AKT signaling pathway) | [123] | |
WT1-AS | Up-regulated | HIF-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) | |
ZEB2-AS1 | Up-regulated | HIF-1α dependent | Gastric cancer (GC) | • Upregulated in GC • Correlated with poor differentiation, lymph node metastasis and distant metastasis | Cell proliferation and growth ↑ Invasion ↑ In vivo tumor growth ↑ | miR-143-5p | The expression of HIF-1α | Sequestration of miRNAs (Down-regulation of miR-143-5p-mediated repression of HIF-1α expression) | [126] |