LncRNA Information
ID EL0582 Name HOTTIP Aliases HOXA-AS6; HOXA13-AS1; NCRNA00213
Species Homo sapiens Chromosome 7 Start site 27198575
End site 27207259 Chain plus Exon NO. 3
Assembly Ensembl Release 89 Class antisense NCBI accession NR_037843
Ensembl ENSG00000243766 Sequence


Disease
Disease Method Sample Expression pattern Dysfunction type Description PMID Source
hepatocelluar carcinoma dual luciferase reporter gene assays HCC tissue specimens, mouse xenograft model up-regulated interaction Tthe miR-192/-204-HOTTIP axis might be an important molecular pathway during hepatic cell tumorigenesis. 26710269
pancreatic cancer microarray, qPCR, Western blot, knockdown etc. cell lines (Panc1, ASPC1, BxPC3 etc.) up-regulated interaction HOTTIP is expressed in pancreatic cancer cell lines and knockdown of HOTTIP by RNA interference (siHOTTIP) in Panc1 pancreatic cancer cells decreased proliferation, induced apoptosis and decreased migration. HOTTIP functions in pancreatic cancer cells are due, in part, to regulation of some HOX genes including HOXA10, HOXB2, HOXA11, HOXA9 and HOXA1. 25912306 Lnc2Cancer
pancreatic ductal adenocarcinoma microarray, qRT-PCR eight human pancreatic ductal adenocarcinoma (PDAC) tissues and four pancreatic tissues. up-regulated expression Functionally, HOTTIP silencing resulted in proliferation arrest by altering cell-cycle progression, and impaired cell invasion by inhibiting epithelial-mesenchymal transition in pancreatic cancer. HOTTIP promotes cell proliferation, invasion, and chemoresistance by modulating HOXA13. Therefore, the HOTTIP/HOXA13 axis is a potential therapeutic target and molecular biomarker for PDAC. 25889214
prostate cancer microarray, RNA-seq, qPCR, Northern bolt, knockdown etc. prostate cancer tissue, cell lines (LNCaP, CWR22Rv1, PC3 etc.) down-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
lung cancer N/A lung cancer cell line A549 and NCI-H446; tissue of lung cancer up-regulated expression Initially, we found that expression of HOTTIP was significantly elevated in 20 cases of lung cancer.Tumor growth in vivo was also suppressed after depletion of HOTTIP in a mouse model of lung cancer. Moreover, depletion of HOTTIP caused cell cycle arrest in G0/G1 phase and induced significant cell apoptosis. 26265284
hepatocelluar carcinoma N/A N/A N/A expression Currently, upregulated HOTTIP and HOXA13 expressions were associated with the prognosis and progression of the hepatocellular carcinoma (HCC). 24531795 LncRNADisease
tongue squamous cell carcinoma qPCR etc. tongue cancer tissue up-regulated expression In our study, results indicated that lncRNA HOTTIP was highly expressed in TSCC compared with adjacent non-malignant tissues and positively correlated with T stage, clinical stage, and distant metastasis in TSCC patients. 26058875 Lnc2Cancer
colorectal cancer qPCR etc. colorectal cancer samples and 21 adjacent non-malignant samples up-regulated expression Our results indicated that lncRNA HOTTIP was highly expressed in CRC compared with adjacent non-malignant tissues (P<0.001), and positively correlated with T stage (T1-2 vs. T3-4, P = 0.001), clinical stage (I-II stages vs. III-IV stages, P = 0.003), and distant metastasis (absent vs. present, P = 0.014) in CRC patients. Furthermore, we also observed that increased lncRNA HOTTIP expression was an unfavorable prognostic factor in CRC patients (P = 0.001), regardless of T stage, distant metastasis and clinical stage. Finally, overexpression of lncRNA HOTTIP was supposed to be an independent poor prognostic factor for CRC patients through multivariate analysis (P = 0.017). 26617875 Lnc2Cancer
osteosarcoma qPCR, knockdown etc osteosarcomas tissues and matched adjacent non-tumor tissues, cell lines(MG-63, HOS) up-regulated expression We found that HOTTIP expression was up-regulated in OS tissues, and correlated with advanced clinical stage and distant metastasis. OS patients with high HOTTIP expression level had poorer overall survival than those with low HOTTIP expression. Multivariable Cox proportional hazards regression analysis suggested that increased HOTTIP expression was an independent prognostic factor of overall survival in OS patients. Moreover, the results of in vitro assays showed that the suppression of HOTTIP in OS cells significantly reduced cell proliferation, migration and invasion ability 26617868 Lnc2Cancer
hepatocelluar carcinoma qPCR, Luciferase reporter assay etc. cell lines (BEL7402, MHCC97H, MHCC97H-Luc) up-regulated regulation In our profiling study, HOTTIP was identified as the most significantly up-regulated lncRNA in human HCCs, even in early stage of HCC formation. HOTTIP is a novel oncogenic lncRNA, which negatively regulated by miR-125b. Overexpression of HOTTIP contributes to hepatocarcinogenesis by regulating the expression of its neighboring protein-coding genes. 25424744 Lnc2Cancer
hepatocelluar carcinoma qPCR, Western blot, knockdown etc. HCC tissue, cell lines (SNU182, SNU449, SNU423, SNU387, SNU475 etc.) up-regulated expression Long noncoding RNA HOTTIP/HOXA13 expression is associated with disease progression and predicts outcome in hepatocellular carcinoma patients. 24114970 LncRNADisease Lnc2Cancer
colorectal cancer qPCR, Western blot, knockdown etc. CRC and adjacent non-tumor colorectal samples, cell lines (DLD-1, SW480, SW620, HCT116) up-regulated interaction We found that overexpression of HOTTIP is correlated with an advanced pathological stage and a larger tumor size. Moreover, functional analyses revealed that the knockdown of HOTTIP expression by small interfering RNA (siRNA) or small hairpin RNA (shRNA) could inhibit cell proliferation and induce cell apoptosis. More importantly, we observed that HOTTIP knockdown induced a marked increase in the number of cells in the G0/G1 phase and a reduction in the number of cells in the S phase in both DLD-1 cells and SW480 cells. An in vivo experiment also revealed that the knockdown of HOTTIP inhibited tumor growth. Western blot and immunohistochemistry analyses indicated that HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. 26678886 Lnc2Cancer
hirschsprung disease qRT-PCR, Small RNA interference colon tissues rom 79 patients with Hirschsprung disease (HSCR) down-regulated expression LncRNA HOTTIP and HOXA13 were significantly down-regulated in HSCR compared to the controls. Meanwhile, the declined extent of their expression levels makes sense between two main phenotype of HSCR. Our study demonstrates that aberrant reduction of HOTTIP and HOXA13, which have a bidirectional regulatory loop, may play an important role in the pathogenesis of HSCR. 26043692
prostate cancer sciliencing or knockdown of HOTTIP prostate cancer tumorigenesis down-regulated N/A down-regulation of HOTTIP and HOXA13 was associated with cell growth and cell cycle. 27064878
 


Function (not disease relevant)
Methods Sample/condition Expression pattern Dysfunction type Description PMID Source
Strand-specific RT-PCR, RNA-FISH, RNA Interference, overexpression, RNA Immunoprecipitation, RNA chromatography Primary human fibroblasts N/A N/A driving histone H3 lysine 4 trimethylation and gene transcription 21423168
 


Interaction
Interaction target Level of interaction Type of interaction Description PMID Source
HOXA RNA-Protein binding HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. 21423168 LncRNADisease
HOXA RNA-Protein binding HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. 21423168 LncRNADisease
WDR5 RNA-Protein binding HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. 21423168 LncRNADisease
WDR5 RNA-Protein binding HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. 21423168 LncRNADisease
HOXA RNA-DNA regulation Recently, another trans-acting lincRNA, called HOTTIP, has been described activating the transcription of several HOXA genes in vivo by recruiting the proteins Mll1 and Wdr5 on the transcription start sites of the 5' HOXA genes. 21423168 LncRNADisease
HOXA RNA-DNA regulation Recently, another trans-acting lincRNA, called HOTTIP, has been described activating the transcription of several HOXA genes in vivo by recruiting the proteins Mll1 and Wdr5 on the transcription start sites of the 5' HOXA genes. 21423168 LncRNADisease
Mll1 RNA-Protein binding Recently, another trans-acting lincRNA, called HOTTIP, has been described activating the transcription of several HOXA genes in vivo by recruiting the proteins Mll1 and Wdr5 on the transcription start sites of the 5' HOXA genes. 21423168 LncRNADisease
Mll1 RNA-Protein binding Recently, another trans-acting lincRNA, called HOTTIP, has been described activating the transcription of several HOXA genes in vivo by recruiting the proteins Mll1 and Wdr5 on the transcription start sites of the 5' HOXA genes. 21423168 LncRNADisease
Wdr5 RNA-Protein binding Recently, another trans-acting lincRNA, called HOTTIP, has been described activating the transcription of several HOXA genes in vivo by recruiting the proteins Mll1 and Wdr5 on the transcription start sites of the 5' HOXA genes. 21423168 LncRNADisease
Wdr5 RNA-Protein binding Recently, another trans-acting lincRNA, called HOTTIP, has been described activating the transcription of several HOXA genes in vivo by recruiting the proteins Mll1 and Wdr5 on the transcription start sites of the 5' HOXA genes. 21423168 LncRNADisease
WDR5 RNA-Protein binding HOTTIP RNA binds the adaptor protein WDR5 directly and targets WDR5/MLL complexes across HOXA, driving histone H3 lysine 4 trimethylation and gene transcription. 21423168
WDR5 RNA-Protein binding HOTTIP was shown to mediate enhancerlike effects on the adjacent genes through a mechanism involving direct interaction with the adaptor protein WDR5. 21831473 LncRNADisease
HOXA DNA-DNA regulation This study identified HOTTIP in association with the promoter regions of downstream 5'HOXA genes. 21831473 LncRNADisease
HOXA RNA-RNA co-expression Knockdown of HOTTIP in foreskin fibroblasts resulted in lower 5’HOXA gene expression. 21874119 LncRNADisease
WDR5 RNA-Protein binding HOTTIP and Mistral recruit chromatin-activating complexes (WDR5/MLL1) in cis to neighboring genes. 22190456 LncRNADisease
FLJ21870 RNA-RNA co-expression Half-sbsRNA1 siRNA increased the levels of SERPINE1 and FLJ21870 mRNAs to 2-to-4.5-fold above normal. 23728290
HOXA gene cluster,miR-125b RNA-DNA, RNA-RNA regulation Knock-down of HOTTIP significantly suppressed the expression of a number of HOXA genes. Furthermore, we identified miR-125b as a post-transcriptional regulator of HOTTIP. 25424744
HOXA13 RNA-Protein regulation Knockdown of HOXA13 by RNA interference (siHOXA13) revealed that HOTTIP promoted PDAC cell proliferation, invasion, and chemoresistance, at least partly through regulating HOXA13. 25889214
HOX gene RNA-DNA regulation HOTTIP does not regulate HOXA13 but plays a role in regulation of several other HOX genes includingHOXA10, HOXB2, HOXA11, HOXA9 and HOXA1. 25912306
HOXA13 RNA-Protein co-expression LncRNA HOTTIP and HOXA13 were significantly down-regulated in HSCR compared to the controls. SiRNA-mediated knock-down of HOTTIP or HOXA13 correlated with decreased levels of each other and both reduced the cell migration and proliferation without affecting cell apoptosis or cell cycle. 26043692
p21 RNA-Protein regulation HOTTIP potentially contributed to CRC cell growth partially through the silencing of p21 expression. 26678886
miR-192 and miR-204 DNA-RNA regulation miR-192 and miR-204 as two microRNAs (miRNAs) suppressing HOTTIP expression via the Argonaute 2 (AGO2)-mediated RNA interference (RNAi) pathway in HCC. The posttranscriptional silencing of HOTTIP by miR-192, miR-204 or HOTTIP siRNAs could significantly suppress viability of HCC cells. The miR-192/-204-HOTTIP axis may interrupt HCC glutaminolysis through GLS1 inhibition. Besides the known targets (multiple 5' end HOX A genes, i.e. HOXA13), glutaminase (GLS1) was identified as a potential downstream target of the miR-192/-204-HOTTIP axis in HCC. 26710269