Role of APR3 in cancer: apoptosis, autophagy, oxidative stress, and cancer therapy

Zhang, Ping; Zhou, Chaoting; Jing, Qiangan; Gao, Yan; Yang, Lei; Li, Yanchun; Du, Jing; Tong, Xiangmin; Wang, Ying

doi:10.1007/s10495-023-01882-w

Cited by 5 publications

(2 citation statements)

References 102 publications

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“…Cell apoptosis plays a vital role in the progress of tumorigenesis and formation, and a cell apoptosis assay was conducted using staining Annexin-FITC/PI to confirm the contribution of the optimal inhibitor in exerting its antitumor activity. As shown in Figure , the percentage of total apoptotic cells (including early stage and late stage of apoptosis) of the control was only 11.40%.…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer

Sun,

Chu,

Zhang

et al. 2024

J. Med. Chem.

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The aberrant activation of the PI3K/mTOR signaling pathway is implicated in various human cancers. Thus, the development of inhibitors targeting mTOR has attracted considerable attention. In this study, we used a structure-based drug design strategy to discover a highly potent and kinaseselective mTOR inhibitor 24 (PT-88), which demonstrated an mTOR inhibitory IC 50 value of 1.2 nM without obvious inhibition against another 195 kinases from the kinase profiling screening. PT-88 displayed selective inhibition against MCF-7 cells (IC 50 : 0.74 μM) with high biosafety against normal cells, in which autophagy induced by mTOR inhibition was implicated. After successful encapsulation in a lipodisc formulation, PT-88 demonstrated favorable pharmacokinetic and biosafety profiles and exerted a large antitumor effect in an MCF-7 subcutaneous bearing nude mice model. Our study shows the discovery of a highly selective mTOR inhibitor using a structure-based drug discovery strategy and provides a promising antitumor candidate for future study and development.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer

Sun,

Chu,

Zhang

et al. 2024

J. Med. Chem.

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“…Preferential association of PTC-containing isoforms with the monosome, and modestly with the light polyribosome fraction, is consistent with our understanding of NMD’s effect on translation (Maquat et al 1981; Nickless, Bailis, and You 2017; Celik et al 2017). ATRAID (also known as APR3), a relatively poorly understood gene implicated to play roles in all- trans retinoic acid-induced apoptosis, osteoblast differentiation and some cancer types (Zhang et al 2023; Ding et al 2015), demonstrates marked patterns of alternative first exon usage across the gradient. The proximal first exon of ATRAID was preferentially spliced into the monosome-associated isoform, which may indicate its reduced translation.…”

Section: Resultsmentioning

confidence: 99%

Long read subcellular fractionation and sequencing reveals the translational fate of full length mRNA isoforms during neuronal differentiation

Ritter,

Draper,

Vollmers

et al. 2024

Preprint

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Alternative splicing (AS) alters the cis-regulatory landscape of mRNA isoforms leading to transcripts with distinct localization, stability and translational efficiency. To rigorously investigate mRNA isoform-specific ribosome association, we generated subcellular fractionation and sequencing (Frac-seq) libraries using both conventional short reads and long reads from human embryonic stem cells (ESC) and neural progenitor cells (NPC) derived from the same ESC. We performedde novotranscriptome assembly from high-confidence long reads from cytosolic, monosomal, light and heavy polyribosomal fractions and quantified their abundance using short reads from their respective subcellular fractions. Almost half of all transcripts exhibited association with particular subcellular fractions relative to the cytosol. Of the multi-isoform genes, 27% and 18% exhibited significant differential isoform sedimentation in ESC and NPC, respectively. Alternative promoter usage and internal exon skipping accounted for the majority of differences between isoforms from the same gene. Random forest classifiers implicated 3’ and 5’ untranslated region (UTR) GC-content and coding sequence (CDS) and UTR lengths as important determinants of isoform-specific sedimentation profiles. Taken together our data demonstrate that alternative mRNA processing within the CDS and UTRs impacts the translational control of mRNA isoforms during stem cell differentiation, and highlights the utility of using a novel long read sequencing-based method to study translational control.

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Ferroptosis mechanisms and its novel potential therapeutic targets for DLBCL

Bian,

Li,

Chen

et al. 2024

Biomedicine & Pharmacotherapy

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Role of APR3 in cancer: apoptosis, autophagy, oxidative stress, and cancer therapy

Cited by 5 publications

References 102 publications

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer

Design, Synthesis, Formulation, and Bioevaluation of Trisubstituted Triazines as Highly Selective mTOR Inhibitors for the Treatment of Human Breast Cancer

Long read subcellular fractionation and sequencing reveals the translational fate of full length mRNA isoforms during neuronal differentiation

Ferroptosis mechanisms and its novel potential therapeutic targets for DLBCL

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