Contribution of histone variants to aneuploidy: a cancer perspective

Data availability statement: The original contributions presented in the study are included in the article's Supplementary Material, available online at: https://www.frontiersin.org/articles/10.3389/fgene.2023.1290903/full#supplementary-material, further inquiries can be directed to the corresponding authors.Copyright © 2023 Ragusa and Vagnarelli. Histone variants, which generally differ in few amino acid residues, can replace core histones (H1, H2A, H2B, and H3) to confer specific structural and functional features to regulate cellular functions. In addition to their role in DNA packaging, histones modulate key processes such as gene expression regulation and chromosome segregation, which are frequently dysregulated in cancer cells. During the years, histones variants have gained significant attention as gatekeepers of chromosome stability, raising interest in understanding how structural and functional alterations can contribute to tumourigenesis. Beside the well-established role of the histone H3 variant CENP-A in centromere specification and maintenance, a growing body of literature has described mutations, aberrant expression patterns and post-translational modifications of a variety of histone variants in several cancers, also coining the term “oncohistones.” At the molecular level, mechanistic studies have been dissecting the biological mechanisms behind histones and missegregation events, with the potential to uncover novel clinically-relevant targets. In this review, we focus on the current understanding and highlight knowledge gaps of the contribution of histone variants to aneuploidy, and we have compiled a database (HistoPloidyDB) of histone gene alterations linked to aneuploidy in cancers of the The Cancer Genome Atlas project.BBSRC grant BB/V013920/1 to PV

Pan-Cancer Analysis Identifies MNX1 and Associated Antisense Transcripts as Biomarkers for Cancer

The identification of diagnostic and prognostic biomarkers is a major objective in improving clinical outcomes in cancer, which has been facilitated by the availability of high-throughput gene expression data. A growing interest in non-coding genomic regions has identified dysregulation of long non-coding RNAs (lncRNAs) in several malignancies, suggesting a potential use as biomarkers. In this study, we leveraged data from large-scale sequencing projects to uncover the expression patterns of the MNX1 gene and its associated lncRNAs MNX1-AS1 and MNX1-AS2 in solid tumours. Despite many reports describing MNX1 overexpression in several cancers, limited studies exist on MNX1-AS1 and MNX1-AS2 and their potential as biomarkers. By employing clustering methods to visualise multi-gene relationships, we identified a discriminative power of the three genes in distinguishing tumour vs. normal samples in several cancers of the gastrointestinal tract and reproductive systems, as well as in discerning oesophageal and testicular cancer histological subtypes. Notably, the expressions of MNX1 and its antisenses also correlated with clinical features and endpoints, uncovering previously unreported associations. This work highlights the advantages of using combinatory expression patterns of non-coding transcripts of differentially expressed genes as clinical evaluators and identifies MNX1, MNX1-AS1, and MNX1-AS2 expressions as robust candidate biomarkers for clinical applicationsD.R. is the recipient of a Kidscan funded PhD studentship and partly supported by Brunel University Londo

Low-energy and low-momentum representation of the virtual Compton scattering amplitude

We perform an expansion of the virtual Compton scattering amplitude for low energies and low momenta and show that this expansion covers the transition from the regime to be investigated in the scheduled photon electroproduction experiments to the real Compton scattering regime. We discuss the relation of the generalized polarizabilities of virtual Compton scattering to the polarizabilities of real Compton scattering.Comment: 13 pages, LaTeX2e/RevTeX, no figure

Complete one-loop analysis of the nucleon's spin polarizabilities

We present a complete one-loop analysis of the four nucleon spin polarizabilities in the framework of heavy baryon chiral perturbation theory. The first non-vanishing contributions to the isovector and first corrections to the isoscalar spin polarizabilities are calculated. No unknown parameters enter these predictions. We compare our results to various dispersive analyses. We also discuss the convergence of the chiral expansion and the role of the delta isobar.Comment: 4 pp, REVTE

Structure analysis of the virtual Compton scattering amplitude at low energies

We analyze virtual Compton scattering off the nucleon at low energies in a covariant, model-independent formalism. We define a set of invariant functions which, once the irregular nucleon pole terms have been subtracted in a gauge-invariant fashion, is free of poles and kinematical zeros. The covariant treatment naturally allows one to implement the constraints due to Lorentz and gauge invariance, crossing symmetry, and the discrete symmetries. In particular, when applied to the $ep\to e'p'\gamma$ reaction, charge-conjugation symmetry in combination with nucleon crossing generates four relations among the ten originally proposed generalized polarizabilities of the nucleon.Comment: 19 pages, LaTeX2e/RevTeX, no figures, original sections IV.-VI. removed, to be discussed in a separate publication, none of the conclusions change

Generalized polarizabilities of the nucleon studied in the linear sigma model (II)

In a previous paper virtual Compton scattering off the nucleon has been investigated in the one-loop approximation of the linear sigma model in order to determine the 3 scalar generalized polarizabilities. We have now extended this work and calculated the 7 vector polarizabilities showing up in the spin-dependent amplitude of virtual Compton scattering. The results fulfill 3 model-independent constraints recently derived. Compared to the constituent quark model there exist enormous differences for some of the vector polarizabilities. At vanishing three-momentum of the virtual photon, the analytical results of the sigma model and of chiral perturbation theory can be related. The influence of the $\pi^{0}$ exchange in the $t$ channel has been discussed in some detail. Besides, the vector polarizabilities determine 2 linear combinations of the third order spin-polarizabilities appearing in real Compton scattering.Comment: 17 pages, 4 figures, latex2e (Revtex), submitted to Z. Phys.

Investigation on the composition of agarose–collagen i blended hydrogels as matrices for the growth of spheroids from breast cancer cell lines

Three-dimensional (3D) cell culture systems mimic the structural complexity of the tissue microenvironment and are gaining increasing importance as they resemble the extracellular matrix (ECM)–cell and cell–cell physical interactions occurring in vivo. Several scaffold-based culture systems have been already proposed as valuable tools for large-scale production of spheroids, but they often suffer of poor reproducibility or high costs of production. In this work, we present a reliable 3D culture system based on collagen I-blended agarose hydrogels and show how the variation in the agarose percentage affects the physical and mechanical properties of the resulting hydrogel. The influence of the different physical and mechanical properties of the blended hydrogels on the growth, size, morphology, and cell motility of the spheroids obtained by culturing three different breast cancer cell lines (MCF-7, MDA-MB-361, and MDA-MB-231) was also evaluated. As proof of concept, the cisplatin penetration and its cytotoxic effect on the tumor spheroids as function of the hydrogel stiffness were also investigated. Noteworthily, the possibility to recover the spheroids from the hydrogels for further processing and other biological studies has been considered. This feature, in addition to the ease of preparation, the lack of cross-linking chemistry and the high re-producibility, makes this hydrogel a reliable biomimetic matrix for the growth of 3D cell structures

Fixed-t subtracted dispersion relations for Compton scattering off the nucleon

We present fixed-$t$ subtracted dispersion relations for Compton scattering off the nucleon at energies $E_\gamma \leq$ 500 MeV, as a formalism to extract the nucleon polarizabilities with a minimum of model dependence. The subtracted dispersion integrals are mainly saturated by $\pi N$ intermediate states in the $s$-channel $\gamma N \to \pi N \to \gamma N$ and $\pi \pi$ intermediate states in the $t$-channel $\gamma \gamma \to \pi \pi \to N \bar N$. For the subprocess $\gamma \gamma \to \pi \pi$, we construct a unitarized amplitude and find a good description of the available data. We show results for Compton scattering using the subtracted dispersion relations and display the sensitivity on the scalar polarizability difference $\alpha - \beta$ and the backward spin polarizability $\gamma_\pi$, which enter directly as fit parameters in the present formalism