Hepatocyte nuclear factor 1 beta: A perspective in cancer

Chandra, Shubhra; Srinivasan, Srilakshmi; Batra, Jyotsna

doi:10.1002/cam4.3676

Cited by 17 publications

(12 citation statements)

References 122 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…43,46 Moreover, over-and down-expression of HNF1B in cancer cells were both associated with cell proliferation. 47,48 This finding was also observed with other genes, including transcription factor (for instance, with the ALDH1A3 or RARB genes), involved in inherited diseases but also cancer development. No clear mechanisms were proposed to explain these counterintuitive results.…”

Section: Discussionsupporting

confidence: 55%

“…Of note, comparable metabolic disturbances were also observed in cancer cells with HNF1B over‐expression 43,46 . Moreover, over‐ and down‐expression of HNF1B in cancer cells were both associated with cell proliferation 47,48 . This finding was also observed with other genes, including transcription factor (for instance, with the ALDH1A3 or RARB genes), involved in inherited diseases but also cancer development.…”

Section: Discussionmentioning

confidence: 57%

See 1 more Smart Citation

Hepatocyte nuclear factor‐1β shapes the energetic homeostasis of kidney tubule cells

et al. 2021

View full text Add to dashboard Cite

Energetic metabolism controls key steps of kidney development, homeostasis, and epithelial repair following acute kidney injury (AKI). Hepatocyte nuclear factor-1β (HNF-1β) is a master transcription factor that controls mitochondrial function in proximal tubule (PT) cells. Patients with HNF1B pathogenic variant display a wide range of kidney developmental abnormalities and progressive kidney fibrosis. Characterizing the metabolic changes in PT cells with HNF-1β deficiency may help to identify new targetable molecular hubs involved in HNF1B-related kidney phenotypes and AKI. Here, we combined 1 H-NMR-based metabolomic analysis in a murine PT cell line with CrispR/Cas9-induced Hnf1b invalidation (Hnf1b −/− ), clustering analysis, targeted metabolic assays, and datamining of published RNA-seq and ChIP-seq dataset to identify the role of HNF-1β in metabolism. Hnf1b −/− cells grown in normoxic conditions display intracellular ATP depletion, increased cytosolic lactate concentration, increased lipid droplet content, failure to use pyruvate for energetic purposes, increased levels of tricarboxylic acid (TCA) cycle intermediates and oxidized glutathione, and a reduction

show abstract

Section: Discussionsupporting

confidence: 55%

Section: Discussionmentioning

confidence: 57%

Hepatocyte nuclear factor‐1β shapes the energetic homeostasis of kidney tubule cells

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Homeodomain transcription factors are shown to frequently be alternatively spliced [ 56 ]. For example, the homeodomain gene HNF1B , which encodes for three protein isoforms A, B and C, has been shown to have different functions with respect to the transcripts, as HNF1B A and B protein isoforms act as transcriptional activators, while HNF1B C protein isoform that lacks the transactivation domain functions as a transcription repressor [ 56 , 57 , 58 ].…”

Section: Discussionmentioning

confidence: 99%

Identification and Characterization of Alternatively Spliced Transcript Isoforms of IRX4 in Prostate Cancer

Fernando

Liyanage

Moradi

et al. 2021

Genes

Self Cite

View full text Add to dashboard Cite

Alternative splicing (AS) is tightly regulated to maintain genomic stability in humans. However, tumor growth, metastasis and therapy resistance benefit from aberrant RNA splicing. Iroquois-class homeodomain protein 4 (IRX4) is a TALE homeobox transcription factor which has been implicated in prostate cancer (PCa) as a tumor suppressor through genome-wide association studies (GWAS) and functional follow-up studies. In the current study, we characterized 12 IRX4 transcripts in PCa cell lines, including seven novel transcripts by RT-PCR and sequencing. They demonstrate unique expression profiles between androgen-responsive and nonresponsive cell lines. These transcripts were significantly overexpressed in PCa cell lines and the cancer genome atlas program (TCGA) PCa clinical specimens, suggesting their probable involvement in PCa progression. Moreover, a PCa risk-associated SNP rs12653946 genotype GG was corelated with lower IRX4 transcript levels. Using mass spectrometry analysis, we identified two IRX4 protein isoforms (54.4 kDa, 57 kDa) comprising all the functional domains and two novel isoforms (40 kDa, 8.7 kDa) lacking functional domains. These IRX4 isoforms might induce distinct functional programming that could contribute to PCa hallmarks, thus providing novel insights into diagnostic, prognostic and therapeutic significance in PCa management.

show abstract

“… † mRNAs encoding the following proteins: CBX3 codes for protein involved in transcriptional silencing (upregulated in cancers); CCN2 codes for connective tissue growth factor; CDH1 is a tumor suppressor gene encoding E-cadherin; ERBB2 codes for HER-2 Receptor Tyrosine Kinase; FOXO1 is a tumor suppressor gene; FZD8 encodes Frizzled Class Receptor 8 which is a receptor for Wnt proteins (Sun et al ( 2021 ); HMGA2 encodes HMG AT-Hook Protein 2, which functions in the regulation of the cell cycle; HMGB1 encodes HMG Box 1, which has both oncogenic and tumor suppression functions; HNF1B encodes Hepatocyte Nuclear Factor 1-β and functions as a tumor suppressor gene or oncogene (Chandra et al ( 2021 ); HOXB3 encodes transcription factor Homeobox B3 (Li et al ( 2019b ); JAK2 encodes Janus Kinase 2 phosphorylating a tyrosine residue; KLF4 is a tumor suppressor gene encoding Kruppel Like Factor 4, but may also act as an oncogene depending on the cellular context; KLF5 encodes Kruppel Like Factor 5 and acts as an oncogene or tumor suppressor gene depending on the cellular context; PAX6 is a tumor suppressor gene encoding transcription factor Paired Box 6; PDGFC codes for Platelet Derived Growth Factor C (promotes angiogenesis); PDPK1 encodes 3-Phosphoinositide-Dependent Protein Kinase-1 (Domrachev et al ( 2021 ); PIK3CA is an oncogene encoding PI3K, subunit p110α; SESN3 encodes sestrin3, stress-induced protein; SP1 encodes Sp1 Transcription Factor that regulates oncogenes and tumor suppressor genes; SPIN1 encodes Spindlin 1 and is considered an oncogene (Janecki et al ( 2018 ); TEAD4 is an oncogene encoding TEA Domain Transcription Factor 4 (Hippo pathway); YBX1 is an oncogene encoding Y-Box Binding Protein 1; YAP1 is an oncogene encoding Yes1 Associated Transcriptional Regulator (Hippo pathway); ZFP36L2 is an oncogene encoding ZFP36 Ring Finger Protein Like 2; YWHAZ is functioning as an oncogene and codes for an adapter protein belonging to the 14-3-3 family …”

Section: Mirnas Targeting Tyms Mrnamentioning

confidence: 99%

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

Matuszyk

2022

Mol Med

View full text Add to dashboard Cite

Background The active metabolite of 5-Fluorouracil (5FU), used in the treatment of several types of cancer, acts by inhibiting the thymidylate synthase encoded by the TYMS gene, which catalyzes the rate-limiting step in DNA replication. The major failure of 5FU-based cancer therapy is the development of drug resistance. High levels of TYMS-encoded protein in cancerous tissues are predictive of poor response to 5FU treatment. Expression of TYMS is regulated by various mechanisms, including involving non-coding RNAs, both miRNAs and long non-coding RNAs (lncRNAs). Aim To delineate the miRNAs and lncRNAs network regulating the level of TYMS-encoded protein. Main body Several miRNAs targeting TYMS mRNA have been identified in colon cancers, the levels of which can be regulated to varying degrees by lncRNAs. Due to their regulation by the MALAT1 lncRNA, these miRNAs can be divided into three groups: (1) miR-197-3p, miR-203a-3p, miR-375-3p which are downregulated by MALAT1 as confirmed experimentally and the levels of these miRNAs are actually reduced in colon and gastric cancers; (2) miR-140-3p, miR-330-3p that could potentially interact with MALAT1, but not yet supported by experimental results; (3) miR-192-5p, miR-215-5p whose seed sequences do not recognize complementary response elements within MALAT1. Considering the putative MALAT1-miRNAs interaction network, attention is drawn to the potential positive feedback loop causing increased expression of MALAT1 in colon cancer and hepatocellular carcinoma, where YAP1 acts as a transcriptional co-factor which, by binding to the TCF4 transcription factor/ β-catenin complex, may increase the activation of the MALAT1 gene whereas the MALAT1 lncRNA can inhibit miR-375-3p which in turn targets YAP1 mRNA. Conclusion The network of non-coding RNAs may reduce the sensitivity of cancer cells to 5FU treatment by upregulating the level of thymidylate synthase.

show abstract

Hepatocyte nuclear factor 1 beta: A perspective in cancer

Cited by 17 publications

References 122 publications

Hepatocyte nuclear factor‐1β shapes the energetic homeostasis of kidney tubule cells

Hepatocyte nuclear factor‐1β shapes the energetic homeostasis of kidney tubule cells

Identification and Characterization of Alternatively Spliced Transcript Isoforms of IRX4 in Prostate Cancer

MALAT1-miRNAs network regulate thymidylate synthase and affect 5FU-based chemotherapy

Contact Info

Product

Resources

About