Jong Chan Hong

The journal retracts the article titled “Autocrine Motility Factor and Its Peptide Derivative Inhibit Triple-Negative Breast Cancer by Regulating Wound Repair, Survival, and Drug Efflux”

Plants monitor daylength to synchronize their flowering time with their surroundings and thus maximize reproductive fitness. In Arabidopsis ( Arabidopsis thaliana ), CONSTANS (CO) activates the expression of FLOWERING LOCUS T ( FT ); this activation is a crucial aspect of the daylength‐dependent regulation of flowering time. Here, we demonstrate that the basic leucine zipper 3 (bZIP3) transcription factor is important for CO‐induced FT expression under long photoperiod conditions in Arabidopsis. We isolated bZIP3 as a CO‐interacting protein by yeast two‐hybrid screening and verified bZIP3–CO complex formation in Arabidopsis through co‐immunoprecipitation assays. The temporal and spatial expression patterns of bZIP3 are very similar to those of CO , and bZIP3 protein levels fluctuate throughout the day, with high abundance in the late afternoon. The bzip3 mutant displayed delayed flowering under long photoperiods, whereas bZIP3 overexpression accelerated flowering regardless of daylength. bZIP3 directly binds to the FT promoter region containing CO‐responsive elements in vivo . FT messenger RNA (mRNA) levels in the bzip3 mutant and bZIP3 overexpression lines correlated with their flowering times and changed only during the daytime. bZIP3 overexpression resulted in significantly lower FT transcript levels in the co mutant background than in the wild type. Furthermore, bZIP3 forms a complex with ASYMMETRIC LEAVES1 (AS1), a CO partner that helps CO induce FT expression. The bzip3 as1 double mutant flowered later than the two single mutants under longer daylengths, and FT mRNA levels were much lower in the double mutant than in the bzip3 single mutant. Collectively, our findings uncover a new layer of photoperiod‐dependent FT regulation in which bZIP3 facilitates CO to activate FT transcription by forming a complex with AS1.

Plants are complex multi-cellular organisms. Each tissue has its unique role and a variety of cell types that contribute to overall function. Single-cell RNA sequencing (scRNA-seq) has revolutionized our ability to study this cellular diversity. This technology allows us to identify rare cell types and understand their functions within the plant. Additionally, spatial transcriptomics provides a gene expression map within tissue and empowers us to see how cells interact and contribute to tissue-specific functions within their spatial context. While spatial transcriptomics has dramatically advanced our understanding of plant biology, it still faces challenges in capturing individual cells’ complete gene expression profiles. Here, we provide a comprehensive overview of scRNA-seq and spatial transcriptomics, including the experimental procedures, computational methods, and data integration strategies. It highlights the impact of these technologies on plant cell biology, discusses their strengths and limitations, and offers a glimpse into the future of this exciting field. As these technologies continue to evolve, they will provide an increasingly detailed and comprehensive view of plant cells, leading to discoveries about plant development, function, and response to the environment.

Climate change threatens global crop yield and food security due to rising temperatures, erratic rainfall, and increased abiotic stresses like drought, heat, and salinity. Gene editing technologies, including CRISPR/Cas9, base editors, and prime editors, offer precise tools for enhancing crop resilience. This review explores the mechanisms of these technologies and their applications in developing climate-resilient crops to address future challenges. While CRISPR/enables targeted modifications of plant DNA, the base editors allow for direct base conversion without inducing double-stranded breaks, and the prime editors enable precise insertions, deletions, and substitutions. By understanding and manipulating key regulator genes involved in stress responses, such as DREB, HSP, SOS, ERECTA, HsfA1, and NHX; crop tolerance can be enhanced against drought, heat, and salt stress. Gene editing can improve traits related to root development, water use efficiency, stress response pathways, heat shock response, photosynthesis, membrane stability, ion homeostasis, osmotic adjustment, and oxidative stress response. Advancements in gene editing technologies, integration with genomics, phenomics, artificial intelligence (AI)/machine learning (ML) hold great promise. However, challenges such as off-target effects, delivery methods, and regulatory barriers must be addressed. This review highlights the potential of gene editing to develop climate-resilient crops, contributing to food security and sustainable agriculture.

Triple-negative breast cancer (TNBC) presents a significant challenge in oncology due to its aggressive nature and limited targeted therapeutic options. This study explores the potential of autocrine motility factor (AMF) and an AMF-derived peptide as novel treatments for TNBC. AMF, primarily secreted by neoplastic cells, plays a crucial role in cancer cell motility, metastasis, and proliferation. The research demonstrates that AMF and its derived peptide inhibit TNBC cell proliferation by modulating cellular migration, redox homeostasis, apoptotic pathways, and drug efflux mechanisms. Dose-dependent antiproliferative effects were observed across three TNBC cell lines, with higher concentrations impairing cellular migration. Mechanistic studies revealed decreased glucose-6-phosphate dehydrogenase expression and elevated reactive oxygen species production, suggesting redox imbalance as a primary mediator of apoptosis. Combination studies with conventional therapeutics showed near-complete eradication of resistant TNBC cells. The observed reduction in p53 levels and increased intranuclear doxorubicin accumulation highlight the AMF/AMF peptide’s potential as multidrug resistance modulators. This study underscores the promise of using AMF/AMF peptide as a novel therapeutic approach for TNBC, addressing current treatment limitations and warranting further investigation.

Heat stress is a substantial and imminent threat to plant growth and development. Understanding its adverse effects on plant development at the molecular level is crucial for sustainable agriculture. However, the molecular mechanism underlying how heat stress causes developmental defects in flowers remains poorly understood. Here, we identified Indole-3-Acetic Acid 8 (IAA8), a repressor of auxin signaling, as a substrate of mitogen-activated protein kinases (MPKs) in Arabidopsis thaliana, and found that MPK-mediated phosphorylation of IAA8 inhibits flower development. MPKs phosphorylated three residues of IAA8: S74, T77, and S135. Interestingly, transgenic plants overexpressing a phospho-mimicking mutant of IAA8 (IAA8^DDD OX) exhibited defective flower development due to high IAA8 levels. Furthermore, MPK-mediated phosphorylation inhibited IAA8 polyubiquitination, thereby significantly increasing its stability. Additionally, the expression of key transcription factors involved in flower development, such as bZIP and MYB genes, was significantly perturbed in the IAA8^DDD OX plants. Collectively, our study demonstrates that heat stress inhibits flower development by perturbing the expression of flower development genes through the MPK-mediated phosphorylation of IAA8, suggesting that Aux/IAA phosphorylation enables plants to fine-tune their development in response to environmental stress.

Context Cyclin-dependent kinase 9 (CDK9) plays a significant role in gene regulation and RNA polymerase II transcription under basal and stimulated conditions. The upregulation of transcriptional homeostasis by CDK9 leads to various malignant tumors and therefore acts as a valuable drug target in addressing cancer incidences. Ongoing drug development endeavors targeting CDK9 have yielded numerous clinical candidate molecules currently undergoing investigation as potential CDK9 modulators, though none have yet received Food and Drug Administration (FDA) approval. Methods In this study, we employ in silico approaches including the molecular docking and molecular dynamics simulations for the virtual screening over the natural compounds library to identify novel promising selective CDK9 inhibitors. The compounds derived from the initial virtual screening were subsequently employed for molecular dynamics simulations and binding free energy calculations to study the compound’s stability under virtual physiological conditions. The first-generation CDK inhibitor Flavopiridol was used as a reference to compare with our novel hit compound as a CDK9 antagonist. The 500-ns molecular dynamics simulation and binding free energy calculation showed that two natural compounds showed better binding affinity and interaction mode with CDK9 receptors over the reference Flavopiridol. They also showed reasonable figures in the predicted absorption, distribution, metabolism, excretion, and toxicity (ADMET) calculations as well as in computational cytotoxicity predictions. Therefore, we anticipate that the proposed scaffolds could contribute to developing potential and selective CDK9 inhibitors subjected to further validations.