Transcription Factor Research Articles

Non-small cell lung carcinoma with co-expression of TTF1 and p40: a clinicopathological analysis of six cases

Objective: To investigate the clinicopathological features, molecular pathology characteristics, and prognosis of non-small cell lung carcinoma (NSCLC) exhibiting co-expression of p40 and thyroid transcription factor1 (TTF1). Methods: Clinical and pathological data of six NSCLC cases with co-expression of p40 and TTF1 diagnosed at the First People's Hospital of Xiaoshan District, Hangzhou, China from January 2016 to December 2023 were collected. Relevant literature was also reviewed. Results: NSCLC with co-expression of p40 and TTF1 commonly occurred in male smokers and had been in stage Ⅲ-Ⅳ when diagnosis. Microscopic examination revealed that the tumor cells were arranged in solid nests and sheets with marked atypia and visible mitotic figures. There was no prominent evidence of keratinization or glandular formation. The tumor cells diffusely co-expressed p40 and TTF1, exhibiting a dual immunophenotype characteristic of both squamous cell carcinoma and adenocarcinoma. Molecular testing of four NSCLC co-expressing p40 and TTF1 revealed the presence of common EGFR mutations, as well as mutations of NRAS (mutation rate of 2.09%), EML4-ALK (mutation rate of 24.77%), and PIK3CA (exon 10 c.1658 G>C p.S553T, mutation rate of 4.32%). All six tumors were poorly differentiated, highly invasive, and associated with poor prognosis. Four of the six patients experienced widespread metastasis and died within 7 to 30 months after the diagnosis or initial treatment. Conclusions: NSCLC with co-expression of p40 and TTF1 exhibits distinct clinicopathological features, immunophenotypes, molecular alterations, and clinical outcomes, characterized by rapid progression and poor prognosis. Pathologists should be vigilant in recognizing this entity to avoid misdiagnosis and missed diagnosis.

Identification of cambium stem cell factors and their positioning mechanism

Wood constitutes the largest reservoir of terrestrial biomass. Composed of xylem, it arises from one side of the vascular cambium, a bifacial stem cell niche that also produces phloem on the opposing side. It is currently unknown which molecular factors endow cambium stem cell identity. Here we show that TRACHEARY ELEMENT DIFFERENTIATION INHIBITORY FACTOR (TDIF) ligand–activated PHLOEM INTERCALATED WITH XYLEM (PXY) receptors promote the expression of CAMBIUM-EXPRESSED AINTEGUMENTA-LIKE (CAIL) transcription factors to define cambium stem cell identity in the Arabidopsis root. By sequestrating the phloem-originated TDIF, xylem-expressed PXY confines the TDIF signaling front, resulting in the activation of CAIL expression and stem cell identity in only a narrow domain. Our findings show how signals emanating from cells on opposing sides ensure robust yet dynamically adjustable positioning of a bifacial stem cell layer.

OsbHLH6, a basic helix-loop-helix transcription factor, confers arsenic tolerance and root-to-shoot translocation in rice.

Arsenic (As) is extremely toxic to plants, posing a serious concern for food safety. Identification of genes responsive to As is significative for figuring out this issue. Here, we identified a bHLH transcription factor OsbHLH6 that was involved in mediating the processes of As tolerance, uptake, and root-to-shoot translocation in rice. The expression of OsbHLH6 gene was strongly induced after 3 and 48 h of arsenite [As(III)] treatment. The OsbHLH6-overexpressed transgenic rice (OE-OsbHLH6) was sensitive to, while the knockout mutant of OsbHLH6 gene (Osbhlh6) was tolerant to As(III) stress by affecting the contents of reactive oxygen species (ROS) and non-protein thiols (NPT), etc. Knockout of OsbHLH6 gene increased significantly the As concentration in roots, but decreased extensively As accumulation in shoots, compared to that in OE-OsbHLH6 and WT plants. The transcripts of phytochelatins (PCs) synthetase encoding genes OsPCS1 and OsPCS2, as well as As(III) transporter encoding genes OsLsi1 and OsABCC1 were greatly abundant in Osbhlh6 mutants than in OE-OsbHLH6 and WT plants under As(III) stress. In contrast, the expression of OsLsi2 gene was extensively suppressed by As(III) in Osbhlh6 mutants. OsbHLH6 acted as a transcriptional activator to bind directly to the promoter and regulate the expression of OsPrx2 gene that encodes a peroxidase precursor. Moreover, overexpression of OsbHLH6 gene resulted in significant change of expression ofamounts of abiotic stress-related genes, which might partially contribute to the As sensitivity of OE-OsbHLH6 plants. These findings may broaden our understanding of the molecular mechanism of OsbHLH6-mediated As response in rice and provide novel useful genes for rice As stress-resistant breeding.

Characterization of single-cell cis-regulatory elements informs implications for cell differentiation.

Cis-regulatory elements (CREs) govern the specific patterns and dynamics of gene expression in cells during development, which are the fundamental mechanisms behind cell differentiation. However, the genomic characteristics of single-cell CREs (scCREs) closely linked to cell differentiation during development remain unclear. To explore this, we systematically analyzed ∼250,000 putative scCREs obtained from snATAC-seq analysis of the developing mouse cerebellum. We found that over 80% of these scCREs show pleiotropic effects, being active in two or more cell types. The pleiotropic degrees of proximal and distal scCREs are positively correlated with the density and diversity of transcription factor (TF) binding motifs and GC content. There is a negative correlation between the pleiotropic degrees of scCREs and their distances to the nearest TSSs, and proximal scCREs display higher relevance strengths than distal ones. Furthermore, both proximal and distal scCREs related to cell differentiation exhibit enhanced sequence-level evolutionary conservation, increased density and diversity of TF binding motifs, elevated GC content, and greater distances from their nearest genes. Together, our findings reveal the general genomic characteristics of putative scCREs and provide insights into the genomic and evolutionary mechanisms by which scCREs regulate cell differentiation during development.

Correction to: Cisplatin-mediated down-regulation of miR-145 contributes to up-regulation of PD-L1 via the c-Myc transcription factor in cisplatin-resistant ovarian carcinoma cells

Correction to: Cisplatin-mediated down-regulation of miR-145 contributes to up-regulation of PD-L1 via the c-Myc transcription factor in cisplatin-resistant ovarian carcinoma cells

A Novel Quinoline Inhibitor of the Canonical NF-κB Transcription Factor Pathway

The NF-κB family of transcription factors is a master regulator of cellular responses during inflammation, and its dysregulation has been linked to chronic inflammatory diseases, such as inflammatory bowel disease. It is therefore of vital importance to design and test new effective NF-κB inhibitors that have the potential to be utilized in clinical practice. In this study, we used a commercial transgenic HeLa cell line as an NF-κB activation reporter to test a novel quinoline molecule, Q3, as a potential inhibitor of the canonical NF-κB pathway. Q3 inhibited NF-κB-induced luciferase in concentrations as low as 5 μM and did not interfere with cell survival or induced cell death. A real-time PCR analysis revealed that Q3 could inhibit the TNF-induced transcription of the luciferase gene, as well as the TNF gene, a known downstream target gene. Immunocytochemistry studies revealed that Q3 moderately interferes with TNF-induced NF-κB nuclear translocation. Moreover, docking and molecular dynamics analyses confirmed that Q3 could potentially modulate transcriptional activity by inhibiting the interaction of NF-κB and DNA. Therefore, Q3 could be potentially developed for further in vivo studies as an NF-κB inhibitor.

Anthrax lethal toxin exerts potent metabolic inhibition of the cardiovascular system

ABSTRACT Bacillus anthracis causes anthrax through a combination of bacterial infection and toxemia. As a major virulence factor of B. anthracis , anthrax lethal toxin (LT) is a zinc-dependent metalloproteinase, exerting its cytotoxicity through proteolytic cleavage of the mitogen-activated protein kinase kinases, thereby shutting down the MAPK pathways. Anthrax lethal toxin induces host lethality mostly by targeting the cardiovascular system. Although the enzymatic activity and the molecular targets of LT have long been known, the detailed mechanisms underlying cellular/tissue/organ toxicity are still poorly understood. In this work, we sought to investigate the mechanism of LT-induced cellular damage in the cardiovascular system. We demonstrate for the first time that anthrax lethal toxin has potent inhibitory effects on the central metabolism of cardiomyocytes and endothelial cells. This is likely due to the observed downregulating of c-Myc expression through the toxin-induced inhibition of the ERK pathway. Since c-Myc is a master transcription factor controlling the expression of many rate-limiting metabolic enzymes in glycolysis and the tricarboxylic acid cycle, LT’s downregulation of c-Myc may lead to the observed bioenergetic collapse, particularly, in cardiomyocytes. Since cardiac cell contraction requires continuous production of large amounts of ATP, potent inhibition of the bioenergetics of cardiomyocytes would be incompatible with life. Thus, LT-induced lethality through targeting cardiomyocytes and endothelial cells appears to be a consequence of a bioenergetic collapse, likely due to the toxin’s potent inhibitory activity on the MEK-ERK-c-Myc-metabolic/bioenergetic axis within these target cells of cardiovascular system. IMPORTANCE Anthrax lethal toxin (LT) is a major virulence factor of Bacillus anthracis , the causative pathogen of anthrax disease. Anthrax lethal toxin is a metalloproteinase that cleaves and inactivates MEKs, thereby shutting down MAPK pathways, leading to host mortality primarily through targeting of the cardiovascular system. However, the detailed mechanisms underlying the toxin’s cellular and tissue toxicity are still poorly understood. Here, we found that anthrax lethal toxin has potent inhibitory activity on glycolysis and oxidative phosphorylation of cardiomyocytes and endothelial cells. These effects appear to be the consequence of downregulation of c-Myc, a master transcription factor that controls many rate-limiting enzymes of glycolysis and the tricarboxylic acid cycle. With the high demand on energy for cardiac contraction, the potent inhibition of cardiomyocyte metabolism by LT would be incompatible with life. This work provides critical insights into why the cardiovascular system is the major in vivo target of LT-induced lethality.

M6A Modification of Profilin-1 in Vascular Smooth Muscle Cells Drives Phenotype Switching and Neointimal Hyperplasia via Activation of the p-ANXA2/STAT3 Pathway.

In-stent restenosis is characterized by a significant reduction in lumen diameter within the stented segment, primarily attributed to excessive proliferation of vascular smooth muscle cells (VSMCs) and neointimal hyperplasia. PFN1 (profilin-1), an actin-sequestering protein extensively studied in amyotrophic lateral sclerosis, remains less explored in neointimal hyperplasia. Utilizing single-cell RNA sequencing alongside data from in-stent restenosis patients and various experimental in-stent restenosis models (swine, rats, and mice), we investigated the role of PFN1 in promoting VSMC phenotype switching and neointimal hyperplasia. Single-cell RNA sequencing of stenotic rat carotid arteries revealed a critical role for PFN1 in neointimal hyperplasia, a finding corroborated in stented swine coronary arteries, in-stent restenosis patients, PFN1SMC-IKO (SMC-specific PFN1 knockout) mice, and PFN1 overexpressed mice. PFN1 deletion was shown to suppress VSMC phenotype switching and neointimal hyperplasia in PFN1SMC-IKO mice subjected to a wire-injured model. To elucidate the observed discordance in PFN1 mRNA and protein levels, we identified that METTL3 (N6-methyladenosine methyltransferase) and YTHDF3 (N6-methyladenosine-specific reader) enhance PFN1 translation efficiency in an N6-methyladenosine-dependent manner, confirmed through experiments involving METTL3 knockout and YTHDF3 knockout mice. Furthermore, PFN1 was mechanistically found to interact with the phosphorylation of ANXA2 (annexin A2) by recruiting Src, promoting the phosphorylation of STAT3, a typical transcription factor known to induce VSMC phenotype switching. This study unveils the significance of PFN1 N6-methyladenosine modification in VSMCs, demonstrating its role in promoting phenotype switching and neointimal hyperplasia through the activation of the p-ANXA2 (phospho-ANXA2)/STAT3 pathway.

Multifunctional Transcription Factor YABBY6 Regulates Morphogenesis, Drought and Cold Stress Responses in Rice

Multifunctional Transcription Factor YABBY6 Regulates Morphogenesis, Drought and Cold Stress Responses in Rice

In Vitro Genome-Wide Identification of Transcription Factor Binding Sites.

DNA affinity purification followed by sequencing (DAP-seq) profiles transcription factor (TF) binding sites in vitro, in which recombinant TF captures the genomic fragments with TF binding sites. Here, I describe the preparation of pre-PCR DNA-seq libraries for 96 TFs, including the expression and purification of recombinant TF, the affinity purification of TF binding fragments, and the sequencing-ready library preparation. Using this method, up to 96 DAP-seq libraries can be prepared in 2days.

Identification and Characterization of EIN3/EIL Transcription Factor Family Members in Pinus massoniana Lamb.

Transcription factors refer to types of proteins that perform significant functions in the process of gene expression regulation. The ethylene insensitive 3/ethylene insensitive 3-like (EIN3/EIL) family, functioning as significant transcription factors regulating ethylene, plays a critical role in the growth and development of plants and participates in the plant’s response to diverse environmental stresses. Pinus massoniana is an excellent native tree with high economic and ecological value. However, the study of EIN3/EIL genes in gymnosperms, for instance, P. massoniana, is still relatively limited. In this research, four putative EIN3/EIL genes were identified in the transcriptome of P. massoniana. Bioinformatics analysis showed that PmEIL genes contain a highly conserved EIN3 domain and other structural features of acidic, proline-rich and glutamine-rich sites. The molecular evolution tree analysis demonstrated that the EIN3/EIL family was partitioned into three categories (A, B, and C), and the number, type, and distribution of conserved motifs grouped in one category were similar. The results of qRT-PCR indicated that the expression levels of PmEIL genes were markedly elevated in needles compared to other tissues. Through the analysis of expression patterns of the PmEIL genes under various stress treatments, it was found that the PmEIL genes could participate in plant hormone stimulation induction, osmosis, drought and other response processes. In addition, PmEIL is a nuclear localization protein. PmEIL1, PmEIL3, and PmEIL4 are transcriptional activators, while PmEIL2 is a transcriptional suppressor. This research provides a basis for further elucidating the function of EIN3/EIL transcription factors in growth, development and stress response of P. massoniana.

Molecular cloning of PRD-like homeobox genes expressed in bovine oocytes and early IVF embryos.

Embryonic genome activation (EGA) is a critical step in early embryonic development, as it marks the transition from relying on maternal factors to the initiation of transcription from embryo's own genome. The factors associated with EGA are not well understood and need further investigation. PRD-like (PRDL) homeodomain transcription factors (TFs) are considered to play crucial roles in this early event during development but these TFs have evolved differently, even within mammalian lineages. Different numbers of PRDL TFs have been predicted in bovine (Bos taurus); however, their divergent evolution requires species-specific confirmation and functional investigations. In this study, we conducted molecular cloning of mRNAs for the PRDL TFs ARGFX, DUXA, LEUTX, NOBOX, TPRX1, TPRX2, and TPRX3 in bovine oocytes or in vitro fertilized (IVF) preimplantation embryos. Our results confirmed the expression of PRDL TF genes in early bovine development at the cDNA level and uncovered their structures. For each investigated PRDL TF gene, we isolated at least one homeodomain-encoding cDNA fragment, indicative of DNA binding and thus potential role in transcriptional regulation in developing bovine embryos. Additionally, our cDNA cloning approach allowed us to reveal breed-related differences in bovine, as evidenced by the identification of a high number of single nucleotide variants (SNVs) across the PRDL class homeobox genes. Subsequently, we observed the prediction of the 9aa transactivation domain (9aaTAD) motif in the putative protein sequence of TPRX3 leading us to conduct functional analysis of this gene. We demonstrated that the TPRX3 overexpression in bovine fibroblast induces not only protein-coding genes but also short noncoding RNAs involved in splicing and RNA editing. We supported this finding by identifying a shared set of genes between our and published bovine early embryo development datasets. Providing full-length cDNA evidence for previously predicted homeobox genes that belong to PRDL class improves the annotation of the bovine genome. Updating the annotation with seven developmentally-important genes will enhance the accuracy of RNAseq analysis with datasets derived from bovine preimplantation embryos. In addition, the absence of TPRX3 in humans highlights the species-specific and TF-specific regulation of biological processes during early embryo development.

Role of the basic leucine zipper transcription factor BATF2 in modulating immune responses and inflammation in health and disease.

Basic leucine zipper transcription factor ATF-like 2 (BATF2) is a transcription factor that is known to exhibit tumor-suppressive activity in cancer cells. Within recent years, however, BATF2 has also emerged as an important transcriptional regulator of the immune system. Through its immunomodulatory function, BATF2 has been implicated in a variety of (patho)physiological processes, including host defense against infection, anti-tumor immunity, and maintenance of tissue inflammatory homeostasis. Below, we discuss recent literature that has provided insight into the role of BATF2 as a transcriptional regulator of immune responses in health and disease, including the cell types that express BATF2, the different diseases in which the immunomodulatory effects of BATF2 have been shown to play a role, and the molecular mechanisms through which BATF2 is thought to exert those effects. In doing so, we highlight that the immunological effects of BATF2 are highly context-dependent, and we point out overlap between the mechanisms of action of BATF2 in infectious disease and non-infectious disease. We also discuss areas of interest for future research, the clinical relevance of better understanding BATF2 function, and potential strategies for therapeutic modulation of BATF2.

Direct conversion of urine-derived cells into functional motor neuron-like cells by defined transcription factors.

Direct cell-type conversion of somatic cells into cell types of interest has garnered great attention because it circumvents rejuvenation and preserves the hallmarks of cellular aging (unlike induced pluripotent stem cells [iPSCs]) and is more suitable for modeling diseases with strong age-related and epigenetic contributions. Fibroblasts are commonly used for direct conversion; however, obtaining these cells requires highly invasive skin biopsies. Urine-derived cells (UDCs) are an alternative cell source and can be obtained via noninvasive procedures. Herein, induced motor neuron-like cells (iMNs) were generated from UDCs by transducing transcription factors involved in motor neuron (MN) differentiation. iMNs exhibited neuronal morphology, upregulation of pan-neuron and MN markers, and MN functionality, including spontaneous calcium oscillation and bungarotoxin-positive neuromuscular junction formation, when co-cultured with myotubes. Altogether, the findings of this study indicated that UDCs can be converted to functional MNs. This technology may allow us to understand disease pathogenesis and progression and discover biomarkers and drugs for MN-related diseases at the population level.

Heterologous Expression of MYB Gene (Rosea1) or bHLH Gene (Delila) from Antirrhinum Increases the Phenolics Pools in Salvia miltiorrhiza

Phenolic acids have health-promoting properties, however, but their low concentrations in Salvia miltiorrhiza limit broader medicinal applications. MYB and bHLH transcription factors activate multiple target genes involved in phenylpropanoid metabolism, thereby enhancing the production of various secondary metabolites. We introduced the MYB transcription factor Antirrhinum Rosea1 (AmROS1) or Delila (AmDEL) into S. miltiorrhiza and observed that antioxidant activity in transgenic plants increased by 1.40 to 1.80-fold. The total content was significantly higher in transformants compared to the controls. Furthermore, heterologous expression of AmROS1 or AmDEL triggered moderate accumulations of rosmarinic acid and salvianolic acid at various growth stages. Levels of total phenolics, total flavonoids, and anthocyanins were significantly elevated. These biological and phytochemical alterations were correlated with the upregulated expression of genes involved in phenolic acid biosynthesis. Our findings demonstrate that AmROS1 and AmDEL function as a transcriptional activator in phenolic acids biosynthesis. This study offers further insights into the heterologous or homologous regulation of phenolics production, potentially enabling its engineering in S. miltiorrhiza.

Androgen Receptor Mediates Dopamine Agonist Resistance by Regulating Intracellular Reactive Oxygen Species in Prolactin-Secreting Pituitary Adenoma.

Aims: Dopamine agonists (DAs) are the first-line treatment for patients with prolactin-secreting pituitary adenoma (PRL adenoma). However, a subset of individuals exhibits poor responses, known as DA resistance. Previous studies have reported that DA resistance is more prevalent in male patients. This study aims to investigate the relationship between androgen receptor (AR) expression and DA resistance, as well as to explore underlying mechanisms of AR-mediated DA resistance. Results: Our results demonstrated that patients with higher AR expression exhibit greater resistance to DA in our cohort of DA-resistant PRL adenoma. Furthermore, AR was found to be involved in cell proliferation, PRL secretion, and resistance to bromocriptine (BRC) both in vitro and invivo. Mechanistically, we demonstrated that intracellular reactive oxygen species (ROS) function as upstream mediators of apoptosis and ferroptosis following BRC treatment. As a ligand-dependent transcription factor, AR could translocate to the nucleus and transcriptionally promote NFE2-like bZIP transcription factor 2 (NRF2) expression, which regulates intracellular ROS levels, thereby enhancing cell viability and conferring DA resistance to pituitary adenoma (PA) cells. Finally, AR targeting agents were used to inhibit AR signaling, downregulate NRF2 transcription, and sensitize PA cells to BRC treatment. Conclusion and Innovation: We demonstrated that AR plays a crucial role in mediating DA resistance in PRL adenoma. Mechanistically, AR promotes cell proliferation and PRL secretion and confers drug resistance by transcriptionally regulating NRF2 expression to maintain redox homeostasis in PA cells. Finally, combining AR targeting agents with BRC shows promise as a therapeutic strategy for treating PRL adenomas. Antioxid. Redox Signal. 00, 000-000.

Genome-Wide Identification of the bHLH Gene Family in Callerya speciosa Reveals Its Potential Role in the Regulation of Isoflavonoid Biosynthesis

Callerya speciosa (Champ. ex Benth.) Schot is a significant leguminous plant valued for its edible tuberous roots, which are a plentiful source of isoflavonoids. Basic helix–loop–helix (bHLH) transcription factors (TFs) have been reported to regulate secondary metabolism in plants, especially flavonoid biosynthesis. However, the bHLH genes in C. speciosa have not yet been reported, and their regulatory role in isoflavonoid biosynthesis remains unexplored. Here, 146 CsbHLH genes were identified in the C. speciosa genome, classifying them into 23 subfamilies based on the gene structures and phylogenetic relationships. All the CsbHLH proteins contained both motifs 1 and 2, whereas motif 8 was only distributed in subgroup III (d + e). Collinearity analysis demonstrated that fragmental replications are the primary driver of CsbHLH evolution, with the majority of duplicated CsbHLH gene pairs experiencing selective pressure. Nine candidate CsbHLH genes were found to play a potential role in regulating isoflavonoid biosynthesis through a combination of gene-to-metabolite correlation analysis and weighted gene co-expression network analysis (WGCNA). Additionally, the cis-regulatory elements and response to MeJA of these nine genes were characterized and confirmed through quantitative real-time PCR (qRT-PCR) analysis. Among them, three CsbHLHs (CsbHLH9, CsbHLH89, and CsbHLH95) were selected for further investigation. Yeast two-hybrid (Y2H), dual-luciferase (LUC) assays, bimolecular fluorescence complementation (BiFC) assays, and transient transformation demonstrated that CsbHLH9 acted as a transcriptional activator through its interaction with CsMYB36 and binding to the promoters of isoflavonoid biosynthesis genes in a MeJA-induced manner, such as CsIFR2, CsI3′H2, and CsCHS4, to promote isoflavonoid (calycosin, calycosin-7-o-glucoside, and formononetin) accumulation. Our results establish a basis for the functional analysis of bHLH genes and investigations into the molecular mechanisms underlying isoflavonoid biosynthesis in C. speciosa.

Nonspecific interactions in transcription regulation and organization of transcriptional condensates

Eukaryotic cells are characterized by a high degree of compartmentalization of their internal contents, which ensures precise and controlled regulation of intracellular processes. During many processes, including different stages of transcription, dynamic membrane-free compartments called biomolecular condensates are formed. Transcription condensates contain various transcription factors and RNA polymerase and are formed by high and low specificity interactions between protein factors, DNA and nearby RNA. This review discusses recent data demonstrating the important role of nonspecific multivalent protein-protein and RNA-protein interactions in the organization and regulation of transcription.

DNA damage-induced EMT controlled by the PARP dependent chromatin remodeler ALC1 promotes DNA repair efficiency through RAD51 in tumor cells.

Epithelial-to-mesenchymal transition (EMT) allows cancer cells to metastasize while acquiring resistance to apoptosis and chemotherapeutic agents with significant implications for patients' prognosis and survival. Despite its clinical relevance, the mechanisms initiating EMT during cancer progression remain poorly understood. We demonstrate that DNA damage triggers EMT and that activation of PARP and the PARP-dependent chromatin remodeler ALC1 (CHD1L) was required for this response. Our results suggest that this activation directly facilitates access to the chromatin of EMT transcriptional factors (TFs) which then initiate cell reprogramming. We also show that EMT-TFs bind to the RAD51 promoter to stimulate its expression and to promote DNA repair by homologous recombination (HR). Importantly, a clinically relevant PARP inhibitor reversed or prevented EMT in response to DNA damage while resensitizing tumor cells to other genotoxic agents. Overall, our observations shed light on the intricate relationship between EMT, DNA damage response, and PARP inhibitors, providing potential insights for in cancer therapeutics.

Understanding cold stress response mechanisms in plants: an overview

Low-temperature stress significantly impacts plant growth, development, yield, and geographical distribution. However, during the long-term process of evolution, plants have evolved complicated mechanisms to resist low-temperature stress. The cold tolerance trait is regulated by multiple pathways, such as the Ca2+ signaling cascade, mitogen-activated protein kinase (MAPK) cascade, inducer of CBF expression 1 (ICE1)-C-repeat binding factor (CBF)-cold-reulated gene (COR) transcriptional cascade, reactive oxygen species (ROS) homeostasis regulation, and plant hormone signaling. However, the specific responses of these pathways to cold stress and their interactions are not fully understood. This review summarizes the response mechanisms of plants to cold stress from four aspects, including cold signal perception and transduction, ICE1-CBF-COR transcription cascade regulation, ROS homeostasis regulation and plant hormone signal regulation. It also elucidates the mechanism of cold stress perception and Ca2+ signal transduction in plants, and proposes the important roles of transcription factors (TFs), post-translational modifications (PTMs), light signals, circadian clock factors, and interaction proteins in the ICE1-CBF-COR transcription cascade. Additionally, we analyze the importance of ROS homeostasis and plant hormone signaling pathways in plant cold stress response, and explore the cross interconnections among the ICE1-CBF-COR cascade, ROS homeostasis, and plant hormone signaling. This comprehensive review enhances our understanding of the mechanism of plant cold tolerance and provides a molecular basis for genetic strategies to improve plant cold tolerance.