HNF1A

The long non-coding RNA (lncRNA) hepatocyte nuclear factor-1 alpha (HNF1A) antisense RNA 1 (HNF1A-AS1) is an important lncRNA for liver growth, development, cell differentiation, and drug metabolism. Like many lncRNAs, HNF1A-AS1 has multiple annotated alternative transcripts in the human genome. Several fundamental biological questions are still not solved: (1) How many transcripts really exist in biological samples, such as liver samples and liver cell lines? (2) What are the expression patterns of different alternative HNF1A-AS1 transcripts at different conditions, including during cell growth and development, after exposure to xenobiotics (such as drugs), and in disease conditions, such as metabolic dysfunction-associated steatotic liver disease (MASLD), alcohol-associated liver disease (ALD) cirrhosis, and obesity? (3) Does the siRNA used in previous studies knock down one or multiple transcripts? (4) Do different transcripts have the same or different functions for gene regulation? The presented data confirm the existence of several annotated HNF1A-AS1 transcripts in liver samples and cell lines, but also identify some new transcripts, which are not annotated in the Ensembl genome database...

OBJECTIVE: Maturity-onset diabetes of the young (MODY) occurs due to mutations in genes involved in pancreatic beta cell function and insulin secretion, has heterogeneous clinical and laboratory features, and account for 1-5% of all diabetes cases. The prevalence and distribution of MODY subtypes vary between countries. The aim of this study was to evaluate the clinical and laboratory characteristics, mutation distribution, and phenotype-genotype relationship in a large case series of pediatric Turkish patients genetically diagnosed with MODY...

Cancer stem cells (CSCs) are believed to be responsible for cancer metastasis and recurrence due to their self-renewal ability and resistance to treatment. However, the mechanisms that regulate the stemness of CSCs remain poorly understood. Recently, evidence has emerged suggesting that long non-coding RNAs (lncRNAs) play a crucial role in regulating cancer cell function in different types of malignancies, including gastric cancer (GC). However, the specific means by which lncRNAs regulate the function of gastric cancer stem cells (GCSCs) are yet to be fully understood...

The report covers the current and past activities of the department Molecular Genetics-Function and Therapy (MGFT) at the Cyprus Institute of Neurology and Genetics (CING), an affiliated Reference Center for the European Reference Network on Rare Endocrine Conditions (Endo-ERN).The presented data is the outcome of > 15 years long standing collaboration between MGFT and endocrine specialists from the local government hospitals and the private sector. Up-to-date > 2000 genetic tests have been performed for the diagnosis of inherited rare endocrine disorders...

UNLABELLED: A subgroup of castration-resistant prostate cancer (CRPC) aberrantly expresses a gastrointestinal (GI) transcriptome governed by two GI-lineage-restricted transcription factors, HNF1A and HNF4G. In this study, we found that expression of GI transcriptome in CRPC correlates with adverse clinical outcomes to androgen receptor signaling inhibitor treatment and shorter overall survival. Bromo- and extra-terminal domain inhibitors (BETi) downregulated HNF1A, HNF4G, and the GI transcriptome in multiple CRPC models, including cell lines, patient-derived organoids, and patient-derived xenografts, while AR and the androgen-dependent transcriptome were largely spared...

The aim of this study was to associate FGFR4 rs1966265 and rs351855 variants with colorectal cancer (CRC) in a Mexican population and to perform in silico analysis. Genomic DNA from 412 healthy individuals and 475 CRC patients was analyzed. In silico analysis was performed using the PolyPhen-V2, GEPIA, GTEx, and Cytoscape platforms. The GA genotype dominant model (GAAA) of rs1966265 and the AA genotype dominant and recessive models of rs351855 were identified as CRC risk factors ( p < 0.05). CRC patients aged ≥ 50 years at diagnosis who consumed alcohol had a higher incidence of the rs351855 GA genotype than the control group ( p < 0...

Maturity-onset diabetes of the young (MODY) is a grouping of monogenic disorders. It is characterized by dominantly inherited, non-insulin-dependent diabetes. MODY is relatively rare, encompassing up to 3.5% in those diagnosed under 30 years of age. Specific types are most commonly treated with sulfonylurea, particularly those identified as HNF4A-MODY and HNF1A-MODY. HNF1B-MODY is another type that is most frequently managed with insulin therapy but lacks a defined precision treatment. We present an 18-year-old, non-obese female patient diagnosed with HNF1B-MODY...

BACKGROUND/OBJECTIVE: Monogenic diabetes is a rare type of diabetes that is commonly misdiagnosed as type 1 or 2 diabetes mellitus, which adversely impacts patient care. Such cases are particularly challenging given the heterogeneity in presentation and overlap with other types of diabetes. As the sole use of meglitinides, especially repaglinide, to treat HNF1A -associated monogenic diabetes has been rarely reported in a few other observational studies, we describe a patient who was treated successfully with repaglinide...

Despite the exact biological role of HNF1 homolog A (HNF1A) in the regulatory mechanism of glioblastoma (GBM), the molecular mechanism, especially the downstream regulation as a transcription factor, remains to be further elucidated. Immunohistochemistry was used to detect the expression and clinical relevance of HNF1A in GBM patients. CCK8, TUNEL, and subcutaneous tumor formation in nude mice were used to evaluate the effect of HNF1A on GBM in vitro and in vivo. The correction between HNF1A and epidermal growth factor receptor pathway substrate 8 (EPS8) was illustrated by bioinformatics analysis and luciferase assay...

We performed the next-generation sequencing (NGS) analysis of a rare grade 1 brain meningioma (angiomatous type) and a common grade 1 spinal meningioma (psammomatous type) and compared their mutation profiling. The data were analysed using the Ion Reporter 5.16 programme (Thermo Fisher Scientific, Waltham, MA). Sequencing analysis identified 10 novel variants and two previously reported variants that were common between these two tumours. Nine variants were missense, which included an insertion in EGFR c.1819_1820insCA, causing frameshifting, and a single nucleotide deletion in HRAS and HNF1A genes, causing frameshifting in these genes...

Hepatocyte nuclear factor-4 alpha (HNF-4A) regulates genes with roles in glucose metabolism and β-cell development. Although pathogenic HNF4A variants are commonly associated with maturity-onset diabetes of the young (MODY1; HNF4A-MODY), rare phenotypes also include hyperinsulinemic hypoglycemia, renal Fanconi syndrome and liver disease. While the association of rare functionally damaging HNF1A variants with HNF1A-MODY and type 2 diabetes is well established owing to robust functional assays, the impact of HNF4A variants on HNF-4A transactivation in tissues including the liver and kidney is less known, due to lack of similar assays...

Genetic polymorphisms that impair VLDL secretion are linked to hepatic steatosis, fibrosis and hepatocellular cancer (HCC). Liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) impairs VLDL assembly, promoting hepatic steatosis and fibrosis, which are attenuated in Mttp-LKO X Fabp1 null (Fabp1/Mttp DKO) mice. Here we examine the impact of impaired VLDL secretion in Mttp-LKO mice on HCC incidence and progression in comparison to Fabp1/Mttp DKO mice. DEN treated Mttp-LKO mice exhibited steatosis with increased tumor burden compared to flox controls, while diethylnitrosamine (DEN)- treated Fabp1/Mttp DKO mice exhibited a paradoxical increase in tumor burden and >50% mortality by 50 weeks...

Pregnancy in women with monogenic diabetes is potentially complex, with significant implications for both maternal and fetal health. Among these, maturity-onset diabetes of the young (MODY) stands out as a prevalent monogenic diabetes subtype frequently encountered in clinical practice. Each subtype of MODY requires a distinct approach tailored to the pregnancy, diverging from management strategies in non-pregnant individuals. Glucokinase MODY (GCK-MODY) typically does not require treatment outside of pregnancy, but special considerations arise when a woman with GCK-MODY becomes pregnant...

Premature ovarian failure (POF) defines the occurrence of ovarian failure prior to the age of 40. It occurs in one out of 100 women but is very rare before age 20 (1:10,000). Maturity-onset diabetes of the young (MODY), caused by mutations in the HNF1A gene, is also a rare disorder; all types of MODY account for 1-2% of adult diabetic cases. These two rare nosologic entities coexisted in an adolescent girl evaluated for delayed puberty. Although this combination could represent a chance association, an interrelation might exist...

The prevalence of youth-onset type 2 diabetes (T2D) and childhood obesity has been rising steadily1 , producing a growing public health concern1 that disproportionately affects minority groups2 . The genetic basis of youth-onset T2D and its relationship to other forms of diabetes are unclear3 . Here we report a detailed genetic characterization of youth-onset T2D by analysing exome sequences and common variant associations for 3,005 individuals with youth-onset T2D and 9,777 adult control participants matched for ancestry, including both males and females...

Differentiation of human induced pluripotent stem cells towards pancreatic islet endocrine cells is a complex process, involving the stepwise modulation of key developmental pathways, such as the Hedgehog signaling inhibition during early differentiation stages. In tandem with this active inhibition, key transcription factors for the islet endocrine cell fate, such as HNF1A, show specific changes in their expression patterns. Here we designed a pilot study aimed at investigating the potential interconnection between HH-signaling inhibition and the increase in the HNF1A expression during early regeneration, by inducing changes in the GLI code...

DNA methylation (DNAm) changes play a key role in regulating gene expression in asthma. To investigate the role of epigenetics and transcriptomics change in asthma, we used publicly available DNAm (asthmatics, n = 96 and controls, n = 46) and gene expression (asthmatics, n = 79 and controls, n = 39) data derived from bronchial epithelial cells (BECs). We performed differential methylation/expression and weighted co-methylation/co-expression network analyses to identify co-methylated and co-expressed modules associated with asthma severity and lung function...

Long non-coding RNAs (lncRNAs) outnumber protein-coding transcripts, but their functions remain largely unknown. In this Review, we discuss the emerging roles of lncRNAs in the control of gene transcription. Some of the best characterized lncRNAs have essential transcription cis-regulatory functions that cannot be easily accomplished by DNA-interacting transcription factors, such as XIST, which controls X-chromosome inactivation, or imprinted lncRNAs that direct allele-specific repression. A growing number of lncRNA transcription units, including CHASERR, PVT1 and HASTER (also known as HNF1A-AS1) act as transcription-stabilizing elements that fine-tune the activity of dosage-sensitive genes that encode transcription factors...

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Paclitaxel resistance is associated with a poor prognosis in non-small cell lung cancer (NSCLC) patients, and currently, there is no promising drug for paclitaxel resistance. In this study, we investigated the molecular mechanisms underlying the chemoresistance in human NSCLC-derived cell lines. We constructed paclitaxel-resistant NSCLC cell lines (A549/PR and H460/PR) by long-term exposure to paclitaxel. We found that triptolide, a diterpenoid epoxide isolated from the Chinese medicinal herb Tripterygium wilfordii Hook F, effectively enhanced the sensitivity of paclitaxel-resistant cells to paclitaxel by reducing ABCB1 expression in vivo and in vitro...