Estrogen Alters the Splicing of Type 1 Corticotropin-Releasing Hormone Receptor in Breast Cancer Cells

Lal, Suchita; Allan, A.; Markovic, Danijela; Walker, Rosemary A.; Macartney, J. C.; Europe-Finner, Nick; Tyson-Capper, Alison; Grammatopoulos, Dimitris K.

doi:10.1126/scisignal.2003926

Cited by 18 publications

(15 citation statements)

References 61 publications

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“…Our sample was a community cohort of adults diagnosed with MDD and, in the majority of individuals, we had information about PTSD history that was sufficient to characterize our sample as relatively low trauma; however, it will be important in future research to include scales assessing history, degree, and type of trauma. In addition, there is evidence that estrogens can influence CRF signaling and CRF 1 regulation 57 , 58 and medications that affect estrogen such as hormone replacement therapy can influence cortisol levels 59 . We did not have information to address the potential confound of differing estrogen levels for our participants in the symptom and rumination analyses, although individuals taking hormone replacement therapy or oral contraceptives were excluded from the sample in the neuropsychological performance analysis.…”

Section: Discussionmentioning

confidence: 99%

Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression

et al. 2018

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Corticotropin-releasing factor signaling through CRF receptor type 1 (CRF1) has been shown to contribute to learning and memory function. A haplotype of alleles T-A-T in a set of common polymorphisms in the gene encoding for CRF1 (CRHR1) has been associated with both depression vulnerability and alterations in cognitive functioning. The present study investigated the relations between the TAT haplotype and specific symptoms of depression, self-reported ruminative behaviors, and neuropsychological performance on a learning and memory task. Participants were adults with major depression with and without psychotic features (N = 406). Associations were examined between TAT haplotype and endorsement of depression symptoms from diagnostic interviews, scores on the rumination response scale (RRS), and verbal memory performance on the California Verbal Learning Test-II (CVLT-II). All analyses included depression subtype, age, and sex as covariates; CVLT-II analyses also included evening cortisol levels. Across the entire sample, carriers of more copies of the TAT haplotype reported greater endorsement of the symptom describing difficulty concentrating and making decisions. In separate subsamples, TAT homozygotes had higher rumination scores on the RRS, both brooding and reflection subscales, and more TAT copies were associated with poorer CVLT-II performance in both total learning and free recall trials. These data demonstrate that the CRHR1 TAT haplotype is associated with cognitive features of depression including difficulty with decision-making, higher rumination, and poorer learning and memory. It will be important in future research to identify the specific molecular mechanisms for CRF1 signaling that contribute to depression-related cognitive dysfunction.

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Section: Discussionmentioning

confidence: 99%

Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression

et al. 2018

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“…Real-time adherent cell proliferation was determined by the label-free xCELLigence Real-Time Cell Analyzer (RTCA) DP instrument (Roche Diagnostics Gesellschaft mit beschränkter Haftung, Basel, Switzerland), which utilizes specialized microtiter culture plates containing an interdigitized gold microelectrode on which cells attach and proliferate. Cell contact with the electrode increases the impedance across these gold arrays and reported as an arbitrary “cell index” value as an indication of confluency and adherence ( 34 ). HESCs were seeded into 16-well plates (E-plate-16; Roche Diagnostics Gesellschaft mit beschränkter Haftung) at a density of 10,000 cells per well and cultured in 10% DCC-FBS until ∼80% confluent.…”

Section: Methodsmentioning

confidence: 99%

The clock protein period 2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells

et al. 2015

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Implantation requires coordinated interactions between the conceptus and surrounding decidual cells, but the involvement of clock genes in this process is incompletely understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK (circadian locomotor output cycles kaput) and brain muscle arnt-like 1 and repressors encoded by PER (Period) and Cryptochrome genes. We show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Down-regulation occurred between 12 and 24 hours following differentiation and coincided with reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter. RNA sequencing revealed that premature inhibition of PER2 by small interfering RNA knockdown leads to a grossly disorganized decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators among the 1121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of 70 midluteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure (Spearman rank test, ρ = −0.3260; P = 0.0046). Thus, PER2 synchronizes endometrial proliferation with initiation of aperiodic decidual gene expression; uncoupling of these events may cause recurrent pregnancy loss.—Muter, J., Lucas, E. S., Chan, Y.-W., Brighton, P. J., Moore, J. D., Lacey, L., Quenby, S., Lam, E. W.-F., Brosens, J. J. The clock protein period 2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells.

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“…The SRSF5 enhances the expression of the MCM family members MCM2 and MCM4, that are involved in the initiation and elongation processes of DNA replication, as well as cell growth and colony formation when transfected in CAL 27 and SCC-9 oral squamous cell carcinoma cell lines (Yang et al, 2018). The SRSF6 is involved in the abnormal alternative splicing of the corticotropin-releasing hormone receptor type 1 (CRH-R1) causing indirect perturbation of oncogenic kinases, such as p38 MAPK, Akt and GSK3β, and accumulation of β-catenin in breast cancer (Lal et al, 2013). Knockdown experiments of SRSF7 in HCT116 colon and A549 lung cancer cell lines revealed the production of an exon 6-lacking isoform of the Fas receptor mRNA, that promotes cell survival (Fu and Wang, 2018).…”

Section: Oncogenic Functions Of Hnrnps and Srsfsmentioning

confidence: 99%

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

Cerasuolo

Buonaguro

Tornesello

2020

Front. Cell Dev. Biol.

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The spliceosomal complex components, together with the heterogeneous nuclear ribonucleoproteins (hnRNPs) and serine/arginine-rich (SR) proteins, regulate the process of constitutive and alternative splicing, the latter leading to the production of mRNA isoforms coding multiple proteins from a single pre-mRNA molecule. The expression of splicing factors is frequently deregulated in different cancer types causing the generation of oncogenic proteins involved in cancer hallmarks. Cervical cancer is caused by persistent infection with oncogenic human papillomaviruses (HPVs) and constitutive expression of viral oncogenes. The aberrant activity of hnRNPs and SR proteins in cervical neoplasia has been shown to trigger the production of oncoproteins through the processing of pre-mRNA transcripts either derived from human genes or HPV genomes. Indeed, hnRNP and SR splicing factors have been shown to regulate the production of viral oncoprotein isoforms necessary for the completion of viral life cycle and for cell transformation. Target-therapy strategies against hnRNPs and SR proteins, causing simultaneous reduction of oncogenic factors and inhibition of HPV replication, are under development. In this review, we describe the current knowledge of the functional link between RNA splicing factors and deregulated cellular as well as viral RNA maturation in cervical cancer and the opportunity of new therapeutic strategies.

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Estrogen Alters the Splicing of Type 1 Corticotropin-Releasing Hormone Receptor in Breast Cancer Cells

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Cited by 18 publications

References 61 publications

Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression

Corticotropin-releasing factor 1 receptor haplotype and cognitive features of major depression

The clock protein period 2 synchronizes mitotic expansion and decidual transformation of human endometrial stromal cells

The Role of RNA Splicing Factors in Cancer: Regulation of Viral and Human Gene Expression in Human Papillomavirus-Related Cervical Cancer

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