Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

LncRNA HAND2-AS1 controls liver cancer stem cell functions and serves as a potential therapy target (ChiRP-Seq)

ABSTRACT: Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal and maintenance are poorly understood. Here we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 is highly conserved to its mouse ortholog lncHand2. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanically, HAND2-AS1 recruits the INO80 complex onto BMPR1A promoter to trigger its expression, leading to the activation of BMP signaling. Importantly, targeting HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs have synergistic anti-tumor effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, which may be a potential target for HCC therapy.

ORGANISM(S): Homo sapiens

PROVIDER: GSE126122 | GEO | 2019/02/06

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

LncRNA HAND2-AS1 controls liver cancer stem cell functions and serves as a potential therapy target (RNA microarray)

Project description:Investigation the RNA profiling in Huh7 cells upon knock-out lncRNA HAND2-AS1 or knock-down INO80 via gene expression microarray analysis Hepatocellular carcinoma (HCC) is the most prevalent liver cancer, characterized by a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may well contribute to both of these pathological properties, but the mechanism underlying their self-renewal and maintenance are poorly understood. Here we identified a long noncoding RNA (lncRNA) termed HAND2-AS1 that is highly expressed in liver CSCs. Human HAND2-AS1 is highly conserved to its mouse ortholog lncHand2. HAND2-AS1 is required for the self-renewal maintenance of liver CSCs to initiate HCC development. Mechanically, HAND2-AS1 recruits the INO80 complex onto BMPR1A promoter to trigger its expression, leading to the activation of BMP signaling. Importantly, targeting HAND2-AS1 by antisense oligonucleotides (ASOs) and BMPR1A by siRNAs have synergistic anti-tumor effects on humanized HCC models. Moreover, knockout of lncHand2 or Bmpr1a in mouse hepatocytes impairs BMP signaling and suppresses the initiation of liver cancer. Our findings reveal that HAND2-AS1 promotes the self-renewal of liver CSCs and drives liver oncogenesis, which may be a potential target for HCC therapy.

2019-02-06 | GSE126121 | GEO

Expression data from CSC and Non-CSC of three HCC cell lines

Project description:Hepatocellular carcinoma (HCC) represents the major subtype of liver cancer, characterized with a high rate of recurrence and heterogeneity. Liver cancer stem cells (CSCs) may account for a hierarchical organization of heterogeneous cancer cells. However, how liver CSCs sustain their self-renewal remains largely unknown. We used microarrays to discover the long non-coding RNAs (lncRNAs) expression underlying cell stem cell (CSC) and non cell stem cell (non-CSC) and identified distinct lncRNAs during this process. We sorted CD13+CD133+ and CD13-CD133- cells from Hep3B, Huh7, and PLC/PRF/5 HCC cell lines as liver CSCs and non-CSCs, then hybridized on Affymetrix microarrays. We sought to identify distinct lncRNAs in liver CSCs.

2015-03-05 | E-GEOD-66529 | biostudies-arrayexpress

Expression data from sgPPARD and sgCtrl of HCC cells

2020-06-09 | GSE152108 | GEO

RNA-sequencing analysis of oncospheres from control and SNORD88B-deficient HCC cells

Project description:To explore the role of small nucleolar RNA, SNORD88B on self-renewal of liver cancer stem cells (CSCs), we enriched contorl or SNORD88B-deficient HCC oncospheres.

2023-06-30 | GSE233520 | GEO

N1-methyladenosine methylations in tRNA drive liver tumorigenesis by PPARδ-mediated cholesterol synthesis

Project description:Increased protein translation plays a critical role in cancer development and treatment1,2. However, the molecular mechanism that is involved in this process remains poorly understood. N1-methyladenosine (m1A) methylation in RNA accounts for regulating mRNA translation in a post-transcriptional manner3,4. Here we show that m1A methylation levels are remarkably elevated in hepatocellular carcinoma (HCC) patient tumor tissues, especially in patients with microscopic vascular invasion (MVI). Moreover, m1A methylation signals are increased in liver cancer stem cells (CSCs) and are negatively correlated with HCC patient survival. Consistently, TRMT6 and TRMT61A, forming m1A methyltransferase complex, are highly expressed in advanced HCC tumors and are negatively correlated with HCC survival. TRMT6/TRMT61A-mediated m1A methylations are required for self-renewal of liver CSCs and tumorigenesis. Mechanistically, TRMT6/TRMT61A-dependent m1A in tRNA boost PPARδ expression, which triggers cholesterol synthesis to activate Hedgehog signaling, driving self-renewal of liver CSCs and tumorigenesis. For potential therapeutic benefit, we further identify a specific inhibitor against TRMT6/TRMT61A complex that exerts effective therapeutic effect on liver cancer with high m1A methylations. Our findings provide novel insights into the function and molecular mechanism of m1A modifications underlying liver tumorigenesis and drug target, which will serve as a new biomarker for HCC and pave a new way to develop more effective therapeutic strategies for HCC patients.

2021-03-01 | GSE147840 | GEO

Expression data from CSC and Non-CSC of three primary HCC samples

2019-07-10 | GSE122420 | GEO

Expression data from CSC and Non-CSC of three HCC cell lines

2015-03-05 | GSE66529 | GEO

snoRNA-sequencing analysis of liver cancer stem cells from human samples

Project description:To explore the role of small nucleolar RNA (snoRNA) on self-renewal of liver cancer stem cells (CSCs), we isolated liver CSCs (CD133+CD13+) and Non-CSCs (CD133-CD13-) from huamn liver tumor tissues.

2023-06-30 | GSE233521 | GEO

CRISPR/Cas9 screens reveal that hexokinase 2 enhances cancer stemness and tumorigenicity

Project description:We identified that HK2 facilitate the maintenance and self-renewal of liver cancer stem cells (CSCs). Moreover, HK2 exerts its function by enhancing the accumulation of acetyl-CoA and epigenetically activating the transcription of acyl-CoA synthetase long chain family member 4 (ACSL4), leading to an increase in fatty acid β-oxidation (FAO) activity.

2022-05-06 | GSE184798 | GEO

Hormone-responsive Bmpr1a maintains myoepithelial integrity during pregnancy

Project description:Myoepithelial and luminal cells synergistically expand in the mammary gland during pregnancy, and this process is precisely governed by hormone-related signaling pathways. The BMP signaling pathway is now known to play crucial roles in all organ systems. However, the functions of BMP signaling in the mammary gland remain unclear. Here, we found that Bmpr1a is upregulated by hormone-induced Sp1 at pregnancy. Using a doxycycline (Dox)-inducible Bmpr1a conditional knockout mouse model, we demonstrated that loss of Bmpr1a results in compromised myoepithelial integrity, reduced mammary stem cells and precocious alveolar differentiation during pregnancy. Mechanistically, Bmpr1a regulates the expression of p63 and Slug, two key regulators of myoepithelial maintenance, through pSmad1/5-Smad4 complexes, and consequently activate P-cadherin during pregnancy. Collectively, these findings identify a novel role of BMP signaling in maintaining the identity of myoepithelial cells and suppressing precocious alveolar formation.

2021-03-05 | GSE164550 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data