JunD accentuates arecoline-induced disruption of tight junctions and promotes epithelial-to-mesenchymal transition by association with NEAT1 lncRNA.

Head and neck cancers are highly prevalent in south-east Asia, primarily due to betel nut chewing. Arecoline, the primary alkaloid is highly carcinogenic; however its role in promoting tumorigenesis by disrupting junctional complexes and increasing risk of metastasis is not well delineated. Subsequently, the effects of low and high concentrations of arecoline on the stability of tight junctions and EMT induction were studied.

Increase in significantly predicts the clinical parameters in patients with rheumatoid arthritis.

This study investigated deregulation of lncRNAs and their associations with clinical parameters in rheumatoid arthritis (RA). LncRNAs were quantified from peripheral blood mono-nuclear cells (PBMCs) and plasma of 82 RA patients with 15 matched controls and from knee fluid of 24 RA patients with ten osteoarthritis controls. Multivariate analyses were performed among lncRNAs and clinical parameters of RA.

E2F1 activates MFN2 expression by binding to the promoter and decreases mitochondrial fission and mitophagy in HeLa cells.

Mitofusin-2 (MFN2) is primarily involved in mitochondrial fusion and participates in diverse biological processes. Several reports show that MFN2 is a target of different miRNAs; however, the transcriptional regulation of MFN2 has not been extensively studied. To gain insight into the transcriptional regulation of MFN2, we expressed E2F transcription factor 1 (E2F1) exogenously and observed that it increased the endogenous expression of MFN2 by binding to its putative promoter region.

-activation of small EDRK-rich factor 2 () promoter by Heat Shock Factor 1.

Heat shock response is an adaptive mechanism of cells characterized by rapid synthesis of a class of proteins popularly known as heat shock proteins (HSPs) by heat-induced activation of Heat Shock Factor 1 (HSF1). In course of our earlier study to show that HSF1 regulates transcription of HYPK (Huntingtin Yeast two-hybrid protein K), a chaperone-like protein, we observed presence of few other genes within 10 kb of promoter. In an attempt to understand whether adjacent genes of are co-regulated, we identified that (small EDRK-rich factor 2), an upstream neighboring gene of is also regulated by heat stress and HSF1.

Huntingtin interacting protein HYPK is a negative regulator of heat shock response and is downregulated in models of Huntington's Disease.

Huntingtin interacting protein HYPK (Huntingtin Yeast Partner K) is an intrinsically unstructured protein having chaperone-like activity and can suppress mutant huntingtin aggregates and toxicity in cell model of Huntington's Disease (HD). Heat shock response is an adaptive mechanism of cells characterized by upregulation of heat shock proteins by heat-induced activation of heat shock factor 1 (HSF1). The trans-activation ability of HSF1 is arrested upon restoration of proteostasis.

Heat Shock Factor 1-Regulated miRNAs Can Target Huntingtin and Suppress Aggregates of Mutant Huntingtin.

Background: Heat shock factor 1 (HSF1) is the master regulator of chaperone network in mammalian cells and can protect cells from adverse effects of misfolded proteins by rapidly inducing expression of multiple heat shock proteins (HSPs) and other cytoprotective proteins. HSF1 also regulates transcription of microRNAs (miRNAs) in heat shock-dependent manner and these miRNAs are likely to regulate diverse cellular processes by acting as downstream effectors of HSF1.

Methods: The study was aimed at understanding the effect of HSF1-regulated miRNAs on huntingtin expression and Huntington's Disease (HD) pathogenesis, if any.

Regulation of mitochondrial morphology and cell cycle by microRNA-214 targeting Mitofusin2.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by the increase in CAG repeats beyond 36 at the exon1 of the gene Huntingtin (HTT). Among the various dysfunctions of biological processes in HD, transcription deregulation due to abnormalities in actions of transcription factors has been considered to be one of the important pathological conditions. In addition, deregulation of microRNA (miRNA) expression has been described in HD.

Delayed Cell Cycle Progression in STHdh(Q111)/Hdh(Q111) Cells, a Cell Model for Huntington's Disease Mediated by microRNA-19a, microRNA-146a and microRNA-432.

Several indirect evidences are available to indicate that abnormalities in cell cycle may contribute to pathogenesis of Huntington's disease (HD). Here, we show that the cell cycle progression in STsdh(Q111)/Hdh(Q111)cells, a cell model of HD, is delayed in S and G2-M phases compared to control STHdhQ7/HdhQ7cells. Expression of 17 genes, like PCNA and CHEK1, was increased in STHdh(Q111)/Hdh(Q111)cells.

Heat shock factor 1 regulates hsa-miR-432 expression in human cervical cancer cell line.

Heat shock response pathway is a conserved defense mechanism of mammalian cells to maintain protein homeostasis against proteotoxic environmental conditions. This is characterized by robust synthesis of molecular chaperones mostly by stress-induced activation of heat shock factor 1 (HSF1). MicroRNAs (miRNAs) are a family of small non-coding RNAs that negatively regulate expression of protein-coding genes.

MicroRNA-432 contributes to dopamine cocktail and retinoic acid induced differentiation of human neuroblastoma cells by targeting NESTIN and RCOR1 genes.

MicroRNA (miRNA) regulates expression of protein coding genes and has been implicated in diverse cellular processes including neuronal differentiation, cell growth and death. To identify the role of miRNA in neuronal differentiation, SH-SY5Y and IMR-32 cells were treated with dopamine cocktail and retinoic acid to induce differentiation. Detection of miRNAs in differentiated cells revealed that expression of many miRNAs was altered significantly.

Transcription regulation of HYPK by Heat Shock Factor 1.

HYPK (Huntingtin Yeast Partner K) was originally identified by yeast two-hybrid assay as an interactor of Huntingtin, the protein mutated in Huntington's disease. HYPK was characterized earlier as an intrinsically unstructured protein having chaperone-like activity in vitro and in vivo. HYPK has the ability of reducing rate of aggregate formation and subsequent toxicity caused by mutant Huntingtin.

Grb2 is regulated by foxd3 and has roles in preventing accumulation and aggregation of mutant huntingtin.

Growth factor receptor protein binding protein 2 (Grb2) is known to be associated with intracellular growth and proliferation related signaling cascades. Huntingtin (Htt), a ubiquitously expressed protein, when mutated, forms toxic intracellular aggregates - the hallmark of Huntington's disease (HD). We observed an elevated expression of Grb2 in neuronal cells in animal and cell models of HD.

MicroRNA-124 targets CCNA2 and regulates cell cycle in STHdh(Q111)/Hdh(Q111) cells.

Mutation in huntingtin (HTT) gene causes Huntington's disease (HD). Expression of many micro RNAs is known to alter in cell, animal models and brains of HD patients, but their cellular effects are not known. Here, we show that expression of microRNA-124 (miR-124) is down regulated in HD striatal mutant STHdh(Q111)/Hdh(Q111) cells, a cell model of HD compared to STHdh(Q7)/Hdh(Q7) cells.