ATP-binding Cassette Genes Research Articles

Decoding the Methylation Patterns of ABC Transporters in Colorectal Cancer

Colorectal cancer (CRC) is a significant global health concern, posing a major threat to morbidity and mortality rates. The molecular mechanisms that drive CRC, particularly the DNA methylation patterns in ATP-binding cassette (ABC) genes, have attracted considerable attention because of their potential roles in CRC drug resistance, initiation, and progression. This study aimed to investigate the methylation patterns of ABC genes in CRC using a high-throughput microarray technology. Microarray methylation data from CRC and adjacent normal tissues were subjected to preprocessing, differential methylation analysis, and correlation analysis using the MethSurv tool for a detailed study of methylation patterns. The study revealed global hypomethylation of 43 ABC transporters and two pseudogenes in CRC compared to normal tissues. Receiver operating characteristic curve analysis identified 369 CpG sites as potential biomarkers for CRC diagnosis, with area under the curve values ranging from acceptable to outstanding. Survival analysis demonstrated the correlation between DNA methylation of individual CpG sites and patient survival probability in colon and rectal adenocarcinoma datasets from The Cancer Genome Atlas. The study provides insights into the epigenetic landscape of ABC genes in CRC, highlighting their potential roles in drug resistance, disease initiation, and progression. The findings offer opportunities for developing innovative therapeutic approaches and improving patient outcomes in the fight against CRC. Further research is needed to validate these results and investigate the functional implications of ABC gene methylation in CRC pathogenesis and treatment response.

An integrative strategy used by the aphid Uroleucon formosanum to counter host sesquiterpene lactone defense: Insights from combined genomic and transcriptomic analysis.

Insect herbivores adapt and develop strategies to counteract plant chemical defenses. The aphid Uroleucon formosanum is a serious sap-sucking pest that infests lettuces containing toxic sesquiterpene lactones (STLs). Herein, we employed a combination of genome sequencing and RNA-seq transcriptome profiling to understand the mechanisms underlying phytotoxin tolerance in U.formosanum. We generated the first chromosome-level genome assembly for U.formosanum, with a total size of 453.26Mb and a scaffold N50 of 33.22Mb. Comparative genomic analyses revealed an enrichment of signals for positive selection and gene family expansion in immune-related pathways. Specifically, the expanded set of heat shock protein70 (HSP70) genes showed upregulation after treatment with lactucin, suggesting that they may play a role in the immune response against STLs. The expression of takeout-like genes and cuticle-associated genes was also significantly increased in the lactucin-treated samples. Additionally, 53 cytochrome P450 monooxygenase, 30 carboxylesterase, 19 glutathione S-transferase, 32 uridine diphosphate glycosyltransferase and 63 ATP-binding cassette (ABC) transporter genes were identified in the U.formosanum genome. CYP4C1, CYP6A13 and 7 ABC genes were strongly upregulated in response to lactucin treatment, indicating the involvement of detoxifying enzymes in the tolerance of U.formosanum to STLs. Our findings suggest that the cuticle barrier, immune response and enzyme-mediated metabolic detoxification jointly enhance the tolerance of U.formosanum to phytotoxins and promote its adaptation to host plants. This study presents a valuable genomic resource and provides insights into insect adaptation to plant chemical challenges and future technological developments for pest management.

Characterization of ATP-binding cassette transporters associated with emamectin benzoate tolerance: from the model insect Drosophila melanogaster to the agricultural pest Spodoptera frugiperda.

Multiple families of detoxification genes, including the increasingly recognized family of ATP-binding cassette (ABC) transporters, work together to influence the toxicity of synthetic insecticides and thus their resistance. Effective management of insecticide resistance requires identification of all toxicity-affecting members from each family of toxicity-related genes. Here, we used emamectin benzoate (EB), ABC transporters and Spodoptera frugiperda as a working case to test whether the strategy of 'from the model insect Drosophila melanogaster to agricultural pests' can identify all or most ABC transporter members related to EB tolerance in S. frugiperda. After confirming the involvement of ABC transporters in the toxicity of EB against fruit fly with the ABC inhibitor verapamil, four ABC transporter genes (DmCG3327, DmCG11147, DmCG4822, and DmCG7627) were found to be involved in EB tolerance using RNA interference-based family-wide functional screening. A combination of phylogenic analysis and a reciprocal TBLASTN search identified five S. frugiperda ABC transporter members as homologs (SfABCC4, SfABCG1, and SfABCG23) or one-way best hits (SfABCG4 and SfABCG20) of the four fly ABC genes. Real-time quantitative polymerase chain reaction (qPCR) analysis found that all five S. frugiperda ABC transporter genes were inducible by EB, and expressed in all the developmental stages and larval tissues, but with significant quantitative differences among stages and tissues. A cytotoxicity assay of ABC-overexpressing Sf9 cell lines showed that all the five S. frugiperda ABC transporter genes made Sf9 cells tolerant to EB. This study not only identifies nine ABC transporter genes related to EB tolerance from D. melanogaster (four genes) and S. frugiperda (five genes), but also demonstrates the utility and effectiveness of the 'model to pests' strategy to identify most toxicity-affecting members from a given family of toxicity-related genes. © 2024 Society of Chemical Industry.

Genome-Wide Characterization of ABC Transporter Genes and Expression Profiles in Red Macroalga Pyropia yezoensis Expose to Low-Temperature.

Pyropia yezoensis is an important economic macroalga widely cultivated in the East Asia countries of China, Korea, and Japan. The ATP-binding cassette (ABC) transporter gene family is one of the largest transporter families in all forms of life involved in various biological processes. The characteristics of ABC transporter genes in P. yezoensis (PyABC) and their functions in stress resistance, however, remain largely unknown. In this study, PyABCs were identified and characterized their expression patterns under low-temperature stress. A total of 48 PyABCs transporters were identified and divided into eight subfamilies, which are mostly predicted as membrane-binding proteins. The cis-elements of phytohormone and low-temperature response were distinguished in promoter sequences of PyABCs. Transcriptome analysis showed that PyABCs are involved in response to low-temperature stress. Among them, 12 PyABCs were significantly up-regulated after 24h of exposure to low temperature (2°C). Further quantitative RT-PCR analysis corroborated the highest expression happened at 24 for detected genes of PyABCC8, PyABCF3, and PyABCI1, extraordinarily for PyABCF3, and followed by decreased expression at 48h. The expression of PyABCI1 was generally low in all tested strains. Whereas, in a strain of P. yezoensis with lower tolerance to low temperature, the expression was observed higher in PyABCC1, PyABCC8, and remarkably high in PyABCF3. This study provided valuable information on ABC gene families in P. yezoensis and their functional characteristics, especially on low-temperature resistance, and would help to understand the adaptive mechanisms of P. yezoensis to adverse environments.

Genome-wide analysis of Citrus medica ABC transporters reveals the regulation of fruit development by CmABCB19 and CmABCC10

ATP-binding cassette (ABC) transporters are vital for plant growth and development as they facilitate the transport of essential molecules. Despite the family's significance, limited information exists about its functional distinctions in Citrus medica. Our study identified 119 genes encoding ABC transporter proteins in the C. medica genome. Through an evolutionary tree and qPCR analysis, two ABC genes, CmABCB19 and CmABCC10, were implicated in C. medica fruit development, showing upregulation in normal fruits compared to malformed fruits. CmABCB19 was found to localize to the plasma membrane of Nicotiana tabacum, exhibiting indole-3-acetic acid (IAA) efflux activity in the yeast mutant strain yap1. CmABCC10, a tonoplast-localized transporter, exhibited efflux of diosmin, nobiletin, and naringin, with rutin influx in strain ycf1. Transgenic expression of CmABCB19 and CmABCC10 in Arabidopsis thaliana induced alterations in auxin and flavonoid content, impacting silique and seed size. This effect was attributed to the modulation of structural genes in the auxin biosynthesis (YUC5/9, CYP79B2, CYP83B1, SUR1) and flavonoid biosynthesis (4CL2/3, CHS, CHI, FLS1/3) pathways. In summary, the functional characterization of CmABCB19 and CmABCC10 illuminates auxin and flavonoid transport, offering insights into their interplay with biosynthetic pathways and providing a foundation for understanding the transporter's role in fruit development.

Aberrant lipid accumulation and retinal pigment epithelium dysfunction in PRCD-deficient mice

Progressive Rod-Cone Degeneration (PRCD) is an integral membrane protein found in photoreceptor outer segment (OS) disc membranes and its function remains unknown. Mutations in Prcd are implicated in Retinitis pigmentosa (RP) in humans and multiple dog breeds. PRCD-deficient models exhibit decreased levels of cholesterol in the plasma. However, potential changes in the retinal cholesterol remain unexplored. In addition, impaired phagocytosis observed in these animal models points to potential deficits in the retinal pigment epithelium (RPE). Here, using a Prcd−/− murine model we investigated the alterations in the retinal cholesterol levels and impairments in the structural and functional integrity of the RPE. Lipidomic and immunohistochemical analyses show a 5-fold increase in the levels of cholesteryl esters (C.Es) and lipid deposits in the PRCD-deficient retina, respectively, indicating alterations in total retinal cholesterol. Furthermore, the RPE of Prcd−/− mice exhibit a 1.7-fold increase in the expression of lipid transporter gene ATP-binding cassette transporter A1 (Abca1). Longitudinal fundus and spectral domain optical coherence tomography (SD-OCT) examinations showed focal lesions and RPE hyperreflectivity. Strikingly, the RPE of Prcd−/− mice exhibited age-related pathological features such as lipofuscin accumulation, Bruch's membrane (BrM) deposits and drusenoid focal deposits, mirroring an Age-related Macular Degeneration (AMD)-like phenotype. We propose that the extensive lipofuscin accumulation likely impairs lysosomal function, leading to the defective phagocytosis observed in Prcd−/− mice. Our findings support the dysregulation of retinal cholesterol homeostasis in the absence of PRCD. Further, we demonstrate that progressive photoreceptor degeneration in Prcd−/− mice is accompanied by progressive structural and functional deficits in the RPE, which likely exacerbates vision loss over time.

Establishing a fluorescence-based technique for ABC transporters functional analysis in metabolism of insecticides in a Lepidopteron

The insecticide resistance development poses challenges to the pest control effectiveness. As phase III detoxification enzyme, ATP-binding cassette (ABC) transporters play a crucial role in conferring resistance by facilitating the elimination of insecticides. However, the precise involvement of ABCs in insecticides metabolism remains unclear. In this study, a competitive assay utilizing microinjection of the ABC substrate Texas Red (TR) was established in Lepidoptera for the first time to investigate the contribution of ABCs to the detoxification process of Cydia pomonella towards lambda-cyhalothrin (LCT) and abamectin (ABM). Results revealed that the elimination of TR was hindered by ABC inhibitor verapamil, LCT, or a combination of both, implying a shared subsets of ABCs involved in the transportation of TR and LCT. Moreover, the application of ABM alone led to marked inhibition of TR elimination, with verapamil not further exacerbating this inhibitory effect, indicating that ABM exhibited a highly competitive ABC substrate characteristic and has a strong interaction with them. Furthermore, silencing key resistance associated ABC genes through RNAi resulted in increased mortality of larvae under LCT or ABM exposure, affecting TR elimination and ATP hydrolysis. These findings imply that ABC genes are critical for the active transport function of ABCs energized by ATP, ultimately reducing larvae tolerance to insecticides. In conclusion, our findings not only validated the feasibility of a competitive bioassay using fluorescent ABC substrate in lepidopteran larvae but also highlighted that ABCs in enhancing the efflux capacity of C. pomonella larvae, facilitating the binding and transportation of insecticides and their metabolites.

Genome wide identification and expression profiling of ATP binding cassette (ABC) transporters gene family in lentil (Lens culinaris Medikus) under aluminium stress condition

Adenosine triphosphate-binding cassette transporters (ABC transporters) are involved in regulating plant growth, development and tolerance to environmental stresses. In this study, a total of 138 ABC transporter genes were identified in the lentil genome that were classified into eight subfamilies. Four lentil ABC transporters from subfamily B and I were clustered together with the previously characterized ABC transporter proteins related to aluminium (Al) detoxification. Lentil ABC transporter genes were distributed across the chromosomes. Tandem duplication was the main driving force for expansion of the ABC gene family. Collinearity of lentil with soybean indicated that ABC gene family is closely linked to Glycine max. ABC genes in the same subfamily showed similar gene structure and conserved motifs. The ABC promoter regions harboured a large number of plant hormones and multiple stress responsive cis-regulatory elements. The qRT-PCR showed that ABC genes had varied expression in roots of lentil at different time points under Al stress. This is the first report on genome wide identification and expression analyses of genes encoding ABC transporter genes in lentil which has provided in-depth insight for future research on evolution and elucidation of molecular mechanisms for aluminium tolerance.

Identification and functional characterization of ABC transporters for selenium accumulation and tolerance in soybean

ATP-binding cassette (ABC) transporters were crucial for various physiological processes like nutrition, development, and environmental interactions. Selenium (Se) is an essential micronutrient for humans, and its role in plants depends on applied dosage. ABC transporters are considered to participate in Se translocation in plants, but detailed studies in soybean are still lacking. We identified 196 ABC genes in soybean transcriptome under Se exposure using next-generation sequencing and single-molecule real-time sequencing technology. These proteins fell into eight subfamilies: 8 GmABCA, 51 GmABCB, 39 GmABCC, 5 GmABCD, 1 GmABCE, 10 GmABCF, 74 GmABCG, and 8 GmABCI, with amino acid length 121–3022 aa, molecular weight 13.50–341.04 kDa, and isoelectric point 4.06–9.82. We predicted a total of 15 motifs, some of which were specific to certain subfamilies (especially GmABCB, GmABCC, and GmABCG). We also found predicted alternative splicing in GmABCs: 60 events in selenium nanoparticles (SeNPs)-treated, 37 in sodium selenite (Na2SeO3)-treated samples. The GmABC genes showed differential expression in leaves and roots under different application of Se species and Se levels, most of which are belonged to GmABCB, GmABCC, and GmABCG subfamilies with functions in auxin transport, barrier formation, and detoxification. Protein-protein interaction and weighted gene co-expression network analysis suggested functional gene networks with hub ABC genes, contributing to our understanding of their biological functions. Our results illuminate the contributions of GmABC genes to Se accumulation and tolerance in soybean and provide insight for a better understanding of their roles in soybean as well as in other plants.

Polymorphisms of the ATP-binding cassette sterol efflux transporter genes g5 and g8 in cardiovascular diseases and type 2 diabetes mellitus

Mutations with a decrease in the expression and function of the of the ATP-binding cassette genes proteins ABCG5 and ABCG8, as the main sterol efflux transporters, lead to the accumulation of xenosterols in plasma associated with changes in the lipid profile, hyperglycemia and the risk of cardiovascular diseases (CVD) and type 2 diabetes mellitus (DM2). The review presents studies of the role of ABCG5/G8 polymorphisms in CVD and DM2. In several studies, including large–scale ones, the influence of ABCG5/G8 variants (rs4245791, rs41360247 rs4299376, rs11887534, rs7598542, rs78451356, etc.) on the risk of coronary heart disease (CHD) was proved, in others – when confirming the association of the risk of CHD with ABCG5 polymorphism, this status for ABCG8 was denied. Since sterol metabolism disorders observed in individuals with DM2 are probably associated with low insulin sensitivity, many authors confirmed the association of variants rs4299376, rs4148211, rs140231607 and rs6720173 of the ABCG5/G8 with the risk of DM2, but some authors did not find such a connection with DM2 for variants rs4299376, rs11887534 and rs4148217 of the ABCG8. A decrease in ABCG5/G8 mRNA expression was observed in DM2 in experimental animals and in humans; on the contrary, overexpression of ABCG5/G8 in db/db mice restored the sensitivity of the liver to insulin, which led to a decrease in fasting glucose, lipids and improved glucose tolerance. The inconsistency of data on the association of ABCG5/G8 gene polymorphism with the risk of CVD and DM2 may probably be due to inter-population differences, which necessitates further study of the contribution of ABCG5/G8 variants to the risk of these diseases.

Identification and expression analysis of ATP-binding cassette (ABC) transporters revealed its role in regulating stress response in pear (Pyrus bretchneideri)

BackgroundATP-binding cassette (ABC) transporter proteins constitute a plant gene superfamily crucial for growth, development, and responses to environmental stresses. Despite their identification in various plants like maize, rice, and Arabidopsis, little is known about the information on ABC transporters in pear. To investigate the functions of ABC transporters in pear development and abiotic stress response, we conducted an extensive analysis of ABC gene family in the pear genome.ResultsIn this study, 177 ABC transporter genes were successfully identified in the pear genome, classified into seven subfamilies: 8 ABCAs, 40 ABCBs, 24 ABCCs, 8 ABCDs, 9 ABCEs, 8 ABCFs, and 80 ABCGs. Ten motifs were common among all ABC transporter proteins, while distinct motif structures were observed for each subfamily. Distribution analysis revealed 85 PbrABC transporter genes across 17 chromosomes, driven primarily by WGD and dispersed duplication. Cis-regulatory element analysis of PbrABC promoters indicated associations with phytohormones and stress responses. Tissue-specific expression profiles demonstrated varied expression levels across tissues, suggesting diverse functions in development. Furthermore, several PbrABC genes responded to abiotic stresses, with 82 genes sensitive to salt stress, including 40 upregulated and 23 downregulated genes. Additionally, 91 genes were responsive to drought stress, with 22 upregulated and 36 downregulated genes. These findings highlight the pivotal role of PbrABC genes in abiotic stress responses.ConclusionThis study provides evolutionary insights into PbrABC transporter genes, establishing a foundation for future research on their functions in pear. The identified motifs, distribution patterns, and stress-responsive expressions contribute to understanding the regulatory mechanisms of ABC transporters in pear. The observed tissue-specific expression profiles suggest diverse roles in developmental processes. Notably, the significant responses to salt and drought stress emphasize the importance of PbrABC genes in mediating adaptive responses. Overall, our study advances the understanding of PbrABC transporter genes in pear, opening avenues for further investigations in plant molecular biology and stress physiology.

Genome-wide analysis of ATP-binding cassette (ABC) transporter in Penaeus vannamei and identification of two ABC genes involved in immune defense against Vibrio parahaemolyticus by affecting NF-κB signaling pathway

The ATP-binding cassette (ABC) transporters have crucial roles in various biological processes such as growth, development and immune defense in eukaryotes. However, the roles of ABC transporters in the immune system of crustaceans remain elusive. In this study, 38 ABC genes were systematically identified and characterized in Penaeus vannamei. Bioinformation analysis revealed that PvABC genes were categorized into ABC A-H eight subfamilies with 17 full-transporters, 11 half transporters and 10 soluble proteins, and multiple immunity-related cis-elements were found in gene promoter regions. Expression analysis showed that most PvABC genes were widely and highly expressed in immune-related tissues and responded to the stimulation of Vibrio parahaemolyticus. To investigate whether PvABC genes mediated innate immunity, PvABCC5, PvABCF1 and PvABCB4 were selected for dsRNA interference experiment. Knockdown of PvABCF1 and PvABCC5 not PvABCB4 increased the cumulative mortality of P. vannamei and bacterial loads in hepatopancreas after infection with V. parahaemolyticus. Further analysis showed that the PvABCF1 and PvABCC5 knockdown decreased expression levels of NF-κB pathway genes and antimicrobial peptides (AMPs). Collectively, these findings indicated that PvABCF1 and PvABCC5 might restrict V. parahaemolyticus challenge by positively regulating NF-κB pathway and then promoting the expression of AMPs, which would contribute to overall understand the function of ABC genes in innate immunity of invertebrates.

Analysis of Genes Associated with Feeding Preference and Detoxification in Various Developmental Stages of Aglais urticae.

Herbivorous insects and host plants have developed a close and complex relationship over a long period of co-evolution. Some plants provide nutrients for insects, but plants' secondary metabolites also influence their growth and development. Urtica cannabina roots and leaves are poisonous, yet Aglais urticae larvae feed on them, so we aimed to clarify the mechanism enabling this interaction. At present, studies on the detoxification mechanism of the A. urticae are rare. In our study, first, we used the A. urticae larval odor selection behavior bioassay and choice feeding preference assay to analyze the feeding preferences of A. urticae on its host plant, U. cannabina. Next, we used transcriptome sequencing to obtain the unigenes annotated and classified by various databases, such as KEGG and GO. In this study, we found that U. cannabina could attract A. urticae larvae to feed via scent, and the feeding preference assay confirmed that larvae preferred U. cannabina leaves over three other plants: Cirsium japonicum, Cannabis sativa, and Arctium lappa. The activity of detoxifying enzymes GST and CarE changed in larvae that had consumed U. cannabina. Furthermore, through transcriptomic sequencing analysis, 77,624 unigenes were assembled from raw reads. The numbers of differentially expressed genes were calculated using pairwise comparisons of all life stages; the expression of detoxification enzyme genes was substantially higher in larvae than in the pupal and adult stages. Finally, we identified and summarized 34 genes associated with detoxification enzymes, such as UDP-glucose 4-epimerase gene, 5 Glutathione S-transferase genes, 4 Carboxylesterase genes, 4 Cytochrome P450 genes, 10 ATP-binding cassette genes, 4 Superoxide dismutase, and Peroxidase. Moreover, we identified 28 genes associated with the development of A. urticae. The qRT-PCR results were nearly consistent with the transcriptomic data, showing an increased expression level of four genes in larvae. Taken together, this study examines the correlation between A. urticae and host plants U. cannabina, uncovering a pronounced preference for A. urticae larvae toward host plants. Consistent with RNA-seq, we investigated the mechanism of A. urticae's interaction with host plants and identified detoxification-related genes. The present study provides theoretical support for studying insect adaptation mechanisms and biological control.

Genome-wide analysis of the ABC gene family in almond and functional predictions during flower development, freezing stress, and salt stress

ABC (ATP-binding cassette) transporter proteins are one of the most extensive protein families known to date and are ubiquitously found in animals, plants, and microorganisms. ABCs have a variety of functions, such as plant tissue development regulation, hormone transport, and biotic and abiotic stress resistance. However, the gene characterization and function of the ABC gene family in almond (Prunus dulcis) have not been thoroughly studied. In this study, we identified 117 PdABC genes using the whole genome of ‘Wanfeng’ almond obtained by sequencing and explored their protein characterization. The PdABC family members were classified into eight subfamilies. The members of the same subfamily had conserved motifs but poorly conserved numbers of exons and introns and were unevenly distributed among the eight subfamilies and on the eight chromosomes. Expression patterns showed that PdABC family members were significantly differentially expressed during almond development, dormant freezing stress, and salt stress. We found that PdABC59 and PdABC77 had extremely high expression levels in pollen. PdABC63 and PdABC64 had high expression levels during almond petal development and multiple stages of flower development. PdABC98 was highly expressed in annual dormant branches after six temperature-freezing stress treatments. PdABC29, PdABC69, and PdABC98 were highly expressed under different concentrations of salt stress. This study preliminarily investigated the expression characteristics of ABC genes in different tissues of almond during flower development, freezing stress and salt stress, and the results will provide a reference for further in-depth research and breeding of almond in the future.

The maize ATP-binding cassette (ABC) transporter ZmMRPA6 confers cold and salt stress tolerance in plants.

ZmMRPA6 was cloned and characterized as the first ATP-binding cassette (ABC) transporter in maize to be proven to participate in cold and salt tolerance. Homologous genes AtABCC4 and AtABCC14 of ZmMRPA6 also responded to salt stress. ATP-binding cassette (ABC) proteins are major transmembrane transporters that play significant roles in plant development against various abiotic stresses. However, available information regarding stress-related ABC genes in maize is minimal. In this study, a maize ABC transporter gene, ZmMRPA6, was identified through genome-wide association analysis (GWAS) for cold tolerance in maize seeds germination and functionally characterized. During germination and seedling stages, the zmmrpa6 mutant exhibited enhanced resistance to cold or salt stress. Mutated of ZmMRPA6 did not affect the expression of downstream response genes related cold or salt response at the transcriptional level. Mass spectrometry analysis revealed that most of the differential proteins between zmmrpa6 and wild-type plants were involved in response to stress process including oxidative reduction, hydrolase activity, small molecule metabolism, and photosynthesis process. Meanwhile, the plants which lack the ZmMRPA6 homologous genes AtABCC4 or AtABCC14 were sensitive to salt stress in Arabidopsis. These results indicated that ZmMRPA6 and its homologous genes play a conserved role in cold and salt stress, and functional differentiation occurs in monocotyledonous and dicotyledonous plants. In summary, these findings dramatically improved our understanding of the function of ABC transporters resistance to abiotic stresses in plants.

Zinc finger proteins and ATP-binding cassette transporter-dependent multidrug resistance.

Multidrug resistance (MDR) remains a significant challenge in cancer treatment, leading to poor clinical outcomes. Dysregulation of ATP-binding cassette (ABC) transporters has been identified as a key contributor to MDR. Zinc finger proteins (ZNPs) are key regulators of transcription and have emerged as potential contributors to cancer drug resistance. Bridging the knowledge gap between ZNPs and MDR is essential to understand a source of heterogeneity in cancer treatment. This review sought to elucidate how different ZNPs modulate the transcriptional regulation of ABC genes, contributing to resistance to cancer therapies. The search was conducted using PubMed, Google Scholar, EMBASE and Web of Science. In addition to ABC-blockers, the transcriptional features regulated by ZNP are expected to play a role in reversing ABC-mediated MDR and predicting the efficacy of anticancer treatments. Among the ZNP-induced epithelial to mesenchymal transition, SNAIL, SLUG and Zebs have been identified as important factors in promoting MDR through activation of ATM, NFκB and PI3K/Akt pathways, exposing the metabolism to potential ZNP-MDR interactions. Additionally, nuclear receptors, such as VDR, ER and PXR have been found to modulate certain ABC regulations. Other C2H2-type zinc fingers, including Kruppel-like factors, Gli and Sp also have the potential to contribute to MDR. Besides reviewing evidence on the effects of ZNP dysregulation on ABC-related chemoresistance in malignancies, significant markers of ZNP functions are discussed to highlight the clinical implications of gene-to-gene and microenvironment-to-gene interactions on MDR prospects. Future research on ZNP-derived biomarkers is crucial for addressing heterogeneity in cancer therapy.

Iminoctadine tris (albesilate) resistance in Geotrichum citri-aurantii and its management

The bis-guanidine fungicide iminoctadine tris (albesilate) (ITA) is widely used to control citrus sour rot pathogen Geotrichum citri-aurantii but its resistance status in the orchards is still unclear. In the present study, ITA resistance in G. citri-aurantii was assessed and resistance mechanisms and its alternative fungicides were explored. ITA resistance frequency in field isolates of G. citri-aurantii collected between 2018 and 2020 from orchards in China was 6.2%. Consecutively culturing on potato dextrose agar (PDA) for 10 generations showed that ITA resistance for field resistant isolates was relatively stable, whereas resistance for the laboratory induced resistant isolates declined by 53.9%. The competitive ability on citrus fruit for resistant isolates was substantially lower than that of the sensitive isolates. Resistance mechanism studies showed that an ATP-binding cassette (ABC) gene (EVM0003677) and two major facilitator superfamily (MFS) genes (EVM0000087 and EVM0003101) might be involved in ITA resistance only in the induced resistant isolates but not in the field resistant isolates. Bioassay of 26 fungicides found that the demethylation inhibitor fungicides metconazole and propiconazole, and the dinitro-aniline fungicide fluazinam were highly effective to ITA-sensitive isolates of G. citri-aurantii and their EC50 values were 0.33, 0.56, and 0.54 mg/L, respectively. The protective control efficacies of ITA, propiconazole, metconazole, and fluazinam all at 400 mg/L were 100%, 60.4%, 33.9%, and 18.5%, respectively. No positive cross resistance was detected between ITA and metconazole, propiconazole or fluazinam. The mixture of ITA and propiconazole at the mass ratio of 9:8 had a synergistic co-toxicity factor of 26. These results have significant implications for our awareness of ITA resistance in orchards and its management.

Genome-wide identification and characterization of ABC transporter superfamily in the legume Cajanus cajan.

Plant ATP-binding cassette (ABC) protein family is the largest multifunctional highly conserved protein superfamily that transports diverse substrates across biological membranes by the hydrolysis of ATP and is also the part of the several other biological processes like cellular detoxification, growth and development, stress biology, and signaling processes. In the agriculturally important legume crop Cajanus cajan, a genome-wide identification and characterization of the ABC gene family was carried out. A total of 159 ABC genes were identified that belong to eight canonical classes CcABCA to CcABCG and CcABCI based on the phylogenetic analysis. The number of genes was highest in CcABCG followed by CcABCC and CcABCB class. A total of 85 CcABC genes were found on 11 chromosomes and 74 were found on scaffold. Tandem duplication was the major driver of CcABC gene family expansion. The dN/dS ratio revealed the purifying selection. The phylogenetic analysis revealed class-specific eight superclades which reflect their functional importance. The largest clade was found to be CcABCG which reflects their functional significance. CcABC proteins were mainly basic in nature and found to be localized in the plasma membrane. The secondary structure prediction revealed the dominance of α-helix. The canonical transmembrane and nucleotide binding domain, signature motif LSSGQ, Walker A, Walker B region, and Q loop were also identified. A class-specific exon-intron pattern was also observed. In addition to core elements, different cis-acting regulatory elements like stress, hormone, and cellular responsive were also identified. Expression profiling of CcABC genes at various developmental stages of different anatomical tissues was performed and it was noticed that CcABCF3, CcABCF4, CcABCF5, CcABCG66, and CcABCI3 had the highest expression. The results of the current study endow us with the further functional analysis of Cajanus ABC in the future.

Genome-wide identification and expression pattern profiling of the ATP-binding cassette gene family in tea plant (Camelliasinensis)

The ATP-binding cassette (ABC) gene family is one of the largest and oldest protein families, consisting of ATP-driven transporters facilitating substrate transportation across cell membranes. However, little is known about the evolution and biological function of the ABC gene family in tea plants. In this study, we performed a genome-wide identification and expression analysis of genes encoding ABC transporter proteins in Camellia sinensis. Our analysis of 170 ABC genes revealed that CsABCs were unevenly distributed across 15 chromosomes, with an amino acid length ranging from 188 to 2489 aa, molecular weight ranging from 20.29 to 277.34 kDa, and an isoelectric point ranging from 4.89 to 10.63. Phylogenetic analysis showed that CsABCs were divided into eight subfamilies, among which the ABCG subfamily was the most abundant. Furthermore, the subcellular localization of CsABCs indicated that they were present in various organelles. Collinearity analysis between the tea plant and Arabidopsis thaliana genomes revealed that the CsABC genes were homologous to the AtABC genes. Large gene fragment duplication analysis identified ten gene pairs as tandem repeats, and interaction network analysis demonstrated that CsABCs interacted with various types of target genes, with protein interactions also occurring within the family. Tissue expression analysis indicated that CsABCs were highly expressed in roots, stems, and leaves and were easily induced by drought and cold stress. Moreover, qRT-PCR analysis of the relative expression level of the gene under drought and cold stress correlated with the sequencing results. Identifying ABC genes in tea plants lays a foundation for the classification and functional analysis of ABC family genes, which can facilitate molecular breeding and the development of new tea varieties.

Genetic Factors Associated with Morphine Consumption in Women Undergoing Laparoscopic Cholecystectomy: A Prospective Cohort Study.

Morphine has been a crucial analgesic agent used perioperatively in various surgical procedures. Genetic factors can lead to morphine dose requirement interpatient variability. Our objective was to determine the contribution of genetic polymorphisms in human μ-opioid receptor gene (OPRM1), ATP binding cassette gene (ABCB1) and rs2952768 to the variation of the perioperative morphine consumption in women undergoing laparoscopic cholecystectomy. This is a prospective cohort study that included 102 adult Arab females undergoing laparoscopic cholecystectomy. The exposures were carrying the genetic variants of OPRM1, ABCB1 and rs2952768. Our primary outcome was total morphine or morphine equivalent dose required perioperatively. The secondary outcomes were pain score during the first 24 hours and adverse drug reactions. A standardized, general anaesthesia was used for all subjects. In addition to the genetic factors, we also investigated non-genetic factors influencing post-operative pain sensitivity and morphine consumption. Both (rs1799971, A>G) in OPRM1 and (rs2952768, T>C) showed statistically significant association with intra-operative total morphine dose requirements. Patients carrying the "G" allele in OPRM1 had a significantly higher total morphine mean rank dose compared to the AA genotype [62.9 vs 47.1, p=0.008]. Furthermore, patients homozygous for the rs2952768 (T>C) minor allele "CC" had a higher mean rank compared to the other genotypes [72.7 vs 50.1, p=0.046]. OPRM1 (rs1799971) and rs2952768 are associated with variation of intra-operative morphine consumption in laparoscopic cholecystectomy. This study was registered at ClinicalTrials.gov, NCT04621864. https://clinicaltrials.gov/ct2/show/NCT04621864.