The lncRNA HHIP-AS1 is required for oncogenic SHH signaling in humans
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ABSTRACT:
PROVIDER: PRJNA590733 | ENA |
REPOSITORIES: ENA
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Project description:Here we show that the non-conserved lncRNA HHIP-AS1 promotes tumorigenesis in human SHH-driven brain tumors, including medulloblastoma, atypical teratoid / rhabdoid tumors (AT/RT). We reveal that GLI2 regulates a bidirectional promoter shared between the well-characterized SHH regulator HHIP and HHIP-AS1. We found a novel regulatory lncRNA mechanism, termed blocking endogenous RNA (beRNA), extending the concept of competing endogenous RNA (ceRNA), where HHIP-AS1 binds its target DYCN1I2 to avoid miRNA-425-based degradation.
2022-05-23 | GSE140741 | GEO
Project description:Long non-coding RNAs (lncRNAs) comprise a diverse class of gene expression regulators with emerging roles in many biological processes including cancer. Here we show that the expression of the lncRNA Hedgehog Interacting Protein Antisense 1 (HHIP-AS1) is a hallmark feature of human SHH-driven tumors. Importantly, loss of HHIP-AS1 leads to reduced tumor growth in SHH-driven tumors in vitro and in vivo. Our results demonstrate the power of cross-entity transcriptome-wide comparisons to identify novel epigenetic–regulatory lncRNA circuitries underlying human cancers.
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Project description:We identified ADIRF-AS1 as a BMAL1-CLOCK regulated circadian lncRNA. Loss of ADIRF-AS1 in U2OS cells altered rhythmicity of clock-controlled genes and expression of genes associated with cell adhesion and the extracellular matrix (ECM) but did not affect neighboring genes in cis. Affinity based enrichment of U2OS ADIRF-AS1-interacting proteins identified all components of the tumor suppressive PBAF (PBRM1/BRG1) complex. Because PBRM1 is a tumor suppressor mutated in 40% of clear cell renal carcinoma (ccRCC) cases, we studied ccRCC 786O cells and also found PBRM1 bound to ADIRF-AS1. Reducing ADIRF-AS1 expression in 786O and A498 ccRCC cells decreased expression of PBAF-suppressed genes, consistent with ADIRF-AS1 acting to antagonize the function of PBAF. Loss of PBRM1, however, rescued PBAF responsive cell cycle genes in ADIRF-AS1 KO 786O ccRCC cells. Importantly, ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant PBRM1 tumors. In this regard, loss of ADIRF-AS1 did not affect in vitro 786O cell growth, but strikingly eliminated in vivo tumorigenesis, which was partially rescued by concurrent loss of PBRM1. This rescue, however, requires Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1 in regulating the ECM. Collectively, our findings suggest that ADIRF-AS1 functions partly to antagonize the tumor suppressive effect of the PBAF complex and behaves as an unforeseen BMAL1-regulated, oncogenic lncRNA.
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Project description:Our data showed that NR2F1-AS1 functions oncogenic roles in gastric cancer (GC), but the underlying molecular mechanism remains largely unknown to date. To explore the function of lncRNA NR2F1-AS1 in gastric cancer, loss-of-function and RNA sequencing studies were performed in SGC7901 cell line. The results showed that depletion of NR2F1-AS1 significantly decreased the expression of VAMP7. Interestingly, VAMP7 was also a target gene of miR-29a-3p. Our data showed that NR2F1-AS1 promotes GC progression through regulating miR-29a/VAMP7 axis.
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Project description:Our study suggested that FAM83H-AS1 was a potential oncogenic driver due to chromosome 8q24 amplification in lung adenocarcinoma. To investigate the molecular mechanism of FAM83H-AS1, we performed high-thoughput RNA sequencing (RNA-Seq) assays after the silence of FAM83H-AS1 in A549 cell lines.
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Project description:LncRNA Hypoxia-inducible factor 1α-antisense 1 (HIF1α-AS1) is located on the antisense strand of the important Hypoxia-inducible factor 1α (HIF1α) gene, but being transcribed in antisense direction along the HIF1α promoter. Here we used the 3’end biotinylated HIF1a-AS1 RNA and a control RNA for RNA Pulldown and searched for interacting proteins in nuclear extracts of human umbilical vein endothelial cells (HUVEC).
2022-09-23 | PXD023512 | Pride
Project description:We identified ADIRF-AS1 as a BMAL1-CLOCK regulated circadian lncRNA. Loss of ADIRF-AS1 in U2OS cells altered rhythmicity of clock-controlled genes and expression of genes associated with cell adhesion and the extracellular matrix (ECM) but did not affect neighboring genes in cis. Affinity based enrichment of U2OS ADIRF-AS1-interacting proteins identified all components of the tumor suppressive PBAF (PBRM1/BRG1) complex. Because PBRM1 is a tumor suppressor mutated in 40% of clear cell renal carcinoma (ccRCC) cases, we studied ccRCC 786O cells and also found PBRM1 bound to ADIRF-AS1. Reducing ADIRF-AS1 expression in 786O and A498 ccRCC cells decreased expression of PBAF-suppressed genes, consistent with ADIRF-AS1 acting to antagonize the function of PBAF. Loss of PBRM1, however, rescued PBAF responsive cell cycle genes in ADIRF-AS1 KO 786O ccRCC cells. Importantly, ADIRF-AS1 expression correlates with survival in human ccRCC, particularly in PBRM1 wild-type, but not mutant PBRM1 tumors. In this regard, loss of ADIRF-AS1 did not affect in vitro 786O cell growth, but strikingly eliminated in vivo tumorigenesis, which was partially rescued by concurrent loss of PBRM1. This rescue, however, requires Matrigel, suggesting a PBRM1-independent function of ADIRF-AS1 in regulating the ECM. Collectively, our findings suggest that ADIRF-AS1 functions partly to antagonize the tumor suppressive effect of the PBAF complex and behaves as an unforeseen BMAL1-regulated, oncogenic lncRNA.
2022-11-16 | GSE199825 | GEO
Project description:M2-like macrophage upregulated lncRNA ADPGK-AS1 regulates macrophage phenotype and modulates the influence of macrophages on lung tumor apoptosis and migration. Here we identified proteins that interact with ADPGK-AS1 that might give insight into how this regulation this is regulated on molecular level. We were able to identify interaction with mitochondrial ribosomal proteins, leading to regulation of mitochondrial oxidative phosphorylation.
2023-08-13 | PXD030605 | Pride
Project description:LncRNA MACC1-AS1 is the antisense RNA of MACC1 mRNA, which is located on the sixth intronic of MACC1 gene. MACC1-AS1 is an oncogenic lncRNA in colorectal cancer. But the function role of MACC1-AS1 in breast cancer is unknown. In the present study, We used MS2-Tagged RNA Affinity Purification and miRNA-Seq to characterize microRNAs that associated with MACC1-AS1 in breast cancer cell line MDA231.
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Project description:The oncogenic transcription factor (c-)Myc is overexpressed in a variety of cancers including subtypes of B cell lymphoma. Here we study long noncoding (lnc)RNAs regulated by Myc, arguing that these lncRNAs may be involved in the very strong effect of Myc on cell proliferation. Using multiple in vitro models and taking into account the kinetics of the response to Myc as well as Myc binding sites we defined two Myc-induced and four Myc-repressed lncRNA candidates. Expression levels of the top Myc-induced lncRNA KTN1-AS1 are low in normal B cell subsets and strongly increased in multiple Myc-positive lymphoma cell lines. In addition, primary lymphoma cases stratified by high or low Myc expression show the expected KTN1-AS1 expression differences. Knockdown of KTN1-AS1 severely impaired the cell growth of multiple Burkitt lymphoma cell lines. Gene expression analysis showed that KTN1-AS1 knockdown affects >300 genes genome wide with a strong enrichment of Myc-target genes involved in metabolism and biosynthesis. In line with this finding, KTN1-AS1 depletion in B cell lymphoma cells caused a substantial decrease of Myc transcript and protein. Thus, our data indicates that KTN1-AS1 overexpression in lymphoma may reinforce high Myc expression at the transcriptional level to activate gene expression programs supporting the high metabolic rate present in lymphoma cells. In conclusion, we identified a novel positive feedback loop between c-Myc and KTN1-AS1 in B cell lymphoma cells. LncRNAs such as KTN1-AS1, that regulate important oncogenic factors in specific cell types, may open new ways to cancer therapy.
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