Transcription Factor Hepatocyte Nuclear Factor-1β (HNF-1β) Regulates MicroRNA-200 Expression through a Long Noncoding RNA

Hajarnis, Sachin; Patel, Vishal; Aboudehen, Karam; Attanasio, Massimo; Cobo-Stark, Patricia; Pontoglio, Marco; Igarashi, Peter

doi:10.1074/jbc.m115.670646

Cited by 43 publications

(40 citation statements)

References 56 publications

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“…32,53 Hnf1β cKO and Dicer cKO mice develop renal cysts with increased levels of Pkd1 and decreased levels of miR-200. 18,19 We found increased expression of Pkd1 mRNA and polycystin-1 in the glomeruli of Zeb2 cKO kidneys after the initial phase of glomerular cyst formation. Although miR-200 expression is repressed by ZEB2 54 and Zeb2 gene is a known target of miR-200 55 in a double-negative feedback loop, we did not observe differential expression of miR-200 in Zeb2 cKO kidneys.…”

Section: Discussionmentioning

confidence: 68%

“…Because aberrant expressions of Zeb2 and miR-200 have been reported in young mice with a cystic kidney phenotype and ZEB2 loss-of-function mutations are associated with an increased risk for renal anomalies in MWS patients, 15,18,19 we hypothesized that ZEB2 plays an important role in early kidney development. To test this hypothesis, we analyzed a Zeb2 floxed conditional knockout (cKO) mouse line 20 as Zeb2 null mice die at E9.5 before kidney development begins.…”

Section: Resultsmentioning

confidence: 99%

“…HNF1B mutations cause glomerulocystic disease in human and Hnf1β mesenchyme specific cKO mice also develops glomerular cysts. 11,31 A recent study shows that the expressions of both Zeb2 and Pkd1 are upregulated in another Hnf1β renal specific knockout mouse model with polycystic kidney disease, 18 suggesting that an optimal and balanced ZEB2 expression in the kidney is required to prevent renal cysts formation.…”

Section: Discussionmentioning

confidence: 99%

“…17 Recently, it has been shown that upregulation of ZEB2 in Hnf1b knockout mice and downregulation of miR-200 in Dicer knockout mice are associated with glomerular and tubular cysts. 18,19 However, no direct link between ZEB2 downregulation and renal cystic disease has been established and the pathological effect of ZEB2 downregulation in early nephrogenesis remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease

Rasouly

Kumar

Chan

et al. 2016

Kidney International

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Primary glomerulocystic kidney disease is a special form of renal cystic disorder characterized by Bowman’s space dilatation in the absence of tubular cysts. ZEB2 is a SMAD-interacting transcription factor involved in Mowat-Wilson syndrome, a congenital disorder with an increased risk for kidney anomalies. Here we show that deletion of Zeb2 in mesenchyme-derived nephrons with either Pax2-cre or Six2-cre causes primary glomerulocystic kidney disease without tubular cysts in mice. Glomerulotubular junction analysis revealed many atubular glomeruli in the kidneys of Zeb2 knockout mice, which explains the presence of glomerular cysts in the absence of tubular dilatation. Gene expression analysis showed decreased expression of early proximal tubular markers in the kidneys of Zeb2 knockout mice preceding glomerular cyst formation, suggesting that defects in proximal tubule development during early nephrogenesis contribute to the formation of congenital atubular glomeruli. At the molecular level, Zeb2 deletion caused aberrant expression of Pkd1, Hnf1β, and Glis3, three genes causing glomerular cysts. Thus, Zeb2 regulates the morphogenesis of mesenchyme-derived nephrons and is required for proximal tubule development and glomerulotubular junction formation. Our findings also suggest that ZEB2 might be a novel disease gene in patients with primary glomerular cystic disease.

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Section: Discussionmentioning

confidence: 68%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease

Rasouly

Kumar

Chan

et al. 2016

Kidney International

View full text Add to dashboard Cite

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“…Transcription factors upstream can regulate miRNA through miRNA-coding LNCRNAs [18][19][20]. This highlights the potential to therapeutically manipulate miRNA through LNCRNAs.…”

Section: Towards Precision Medicine In Diabetic Kidney Disease?mentioning

confidence: 99%

Long non-coding RNAs–towards precision medicine in diabetic kidney disease?

Panchapakesan

Pollock

2016

Clinical Science

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Diabetic kidney disease (DKD) is escalating and is the major cause of end stage kidney failure. There is increasing evidence to support the role of epigenetic factors and metabolic memory in linking the environmental and genetic causes of this disease. Although our understanding of this disease has improved, there has been no significant efficacious therapeutic translation in the last decade. Current sequencing technology has allowed interrogation of the human transcriptome. It is evident that although approximately 80 % of the genome is transcribed, only 1-2 % is read and coded into protein. The remaining non-coding RNA, historically assumed to be 'junk', is now known to have key roles in regulating gene function and orchestrate how and when coding genes are expressed. This largest subset of non-coding RNAs called long non-coding RNAs (LNCRNAs) drives epigenetic changes and has functional relevance best characterized in cancers and cardiovascular disease. This understanding, coupled with the availability and affordability of RNA sequencing, has shifted our therapeutic strategies towards genomic therapy in DKD. The role of LNCRNAs with respect to DKD is only just emerging. In this review we summarize the role of LNCRNAs in DKD and the existing antisense oligonucleotide therapy that may provide precise and targeted medicine to treat DKD in this postgenomic era.

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Expression of Concern: HOXD‐AS1/miR‐130a sponge regulates glioma development by targeting E2F8

Chen

Zhao

Cui

et al. 2018

Intl Journal of Cancer

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Glioma development is an extremely complex process with changes occurring in numerous genes. HOXD antisense growth-associated long noncoding RNA (HOXD-AS1), an important long noncoding RNA (lncRNA), is known to regulate metastasis-related gene expression in bladder cancer, ovarian cancer and neuroblastoma. Here, we elucidated the function and possible molecular mechanisms of lncRNA HOXD-AS1 in human glioma cells. Our results proved that HOXD-AS1 expression was upregulated in glioma tissues and in glioma cell lines. HOXD-AS1 overexpression promoted cell migration and invasion in vitro, whereas knockdown of HOXD-AS1 expression repressed these cellular processes. Mechanistic studies further revealed that HOXD-AS1 could compete with the transcription factor E2F8 to bind with miR-130a, thus affecting E2F8 expression. Additionally, reciprocal repression was observed between HOXD-AS1 and miR-130a, and miR-130a mediated the tumor-suppressive effects of HOXD-AS1 knockdown. Taken together, these results provide a comprehensive analysis of the role of HOXD-AS1 in glioma cells and offer important clues to understand the key roles of competing endogenous RNA (ceRNA) mechanisms in human glioma.

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Transcription Factor Hepatocyte Nuclear Factor-1β (HNF-1β) Regulates MicroRNA-200 Expression through a Long Noncoding RNA

Abstract: Background: Transcription factor HNF-1␤ regulates epithelia-specific gene expression.

Cited by 43 publications

References 56 publications

Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease

Loss of Zeb2 in mesenchyme-derived nephrons causes primary glomerulocystic disease

Long non-coding RNAs–towards precision medicine in diabetic kidney disease?

Expression of Concern: HOXD‐AS1/miR‐130a sponge regulates glioma development by targeting E2F8

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