Current Issues in Molecular Biology

Androgens have been shown to be linked to cancer progression, particularly in hormone-dependent cancers such as prostate and breast cancer, but also other cancers. Amyloid precursor protein (APP), which has primarily been studied in Alzheimer’s disease, is gaining recognition for its role in tumor growth and survival. While APP overexpression and androgen receptor (AR) signaling are each associated with cancer progression, the connection between androgens and APP processing in cancer has not been thoroughly investigated. This systematic review was conducted through a comprehensive search of PubMed, Scopus, Web of Science, and EMBASE between 2000 to 2024 for studies examining the effects of androgens on APP and its cleavage enzymes in cancer. Five experimental studies met the inclusion criteria, covering prostate and breast cancer models. Data were extracted and synthesized narratively due to heterogeneity in methods and outcomes. Three studies reported that dihydrotestosterone (DHT) or AR agonists increased the expression and nuclear translocation of ADAM10, a key α-secretase enzyme in the non-amyloidogenic APP processing pathway. Two studies identified APP as an androgen-responsive gene, showing that androgens upregulated APP expression in prostate and breast cancer cells and promoted the proliferation of cancer cells. Inhibition or knockdown of APP and ADAM10 reduced proliferation, supporting their roles in tumor progression. Androgen signaling modulates APP processing in cancer, particularly through the non-amyloidogenic pathway; however, significant knowledge gaps remain. Further studies are needed to explore the interaction between androgens and APP processing in other cancer types, as well as to elucidate downstream signaling pathways regulated at the gene expression level.

Drought stress, exacerbated by climate change, is a serious threat to global food security. This review examines the synergistic potential of plant growth-promoting rhizobacteria (PGPR) and biochar as a sustainable strategy for enhancing crop drought resilience. Biochar’s porous structure creates a protective “charosphere” microhabitat, enhancing PGPR colonization and survival. This partnership, in turn, induces multifaceted plant responses through: (1) the modulation of key phytohormones, including abscisic acid (ABA), ethylene (via 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity), and auxins; (2) improved nutrient solubilization and uptake; and (3) the activation of robust antioxidant defense systems. These physiological benefits are orchestrated by a profound reprogramming of the plant transcriptome, which shifts the plant’s expression profile from a stressed to a resilient state by upregulating key genes (e.g., Dehydration-Responsive Element-Binding protein (DREB), Light-Harvesting Chlorophyll B-binding protein (LHCB), Plasma membrane Intrinsic Proteins (PIPs)) and downregulating stress-senescence markers. To realize a climate-resilient farming future, research must be strategically directed toward customizing biochar–PGPR combinations, validating their long-term performance in agronomic environments, and uncovering the molecular bases of their action.

Analysis of coding areas has long been used to study monogenic illnesses, but despite the extensive use of whole-exome sequencing (WES), up to half of suspected cases remain genetically unexplained. Variants outside coding areas can alter splicing, transcript stability, or gene regulation, compromising normal gene activity. These include mutations in noncoding RNAs, promoters, enhancers, deep intronic sequences, and untranslated regions (UTRs). Several well-known disorders have been linked to these mechanisms, including β-thalassemia caused by deep intronic mutations leading to aberrant splicing, familial hypercholesterolemia caused by promoter defects affecting LDLR expression, and inherited retinal diseases driven by noncoding variants influencing retinal gene regulation. These instances show that pathogenic variation is not limited to the exome and can have significant clinical implications. This review summarizes current understanding of noncoding and regulatory variants in monogenic diseases, discusses how they influence diagnosis and therapy, and highlights integrative approaches combining genomic, transcriptomic, and epigenomic data. Multi-layered research has increased diagnostic accuracy and unveiled new therapeutic potentials, although noncoding variations make the connection between genotype and phenotype more complex. Noncoding regions will need to be incorporated into standard diagnostic procedures to convert molecular insights into concrete therapeutic applications in the future. Predictive algorithms, patient-derived model systems, and functional validation testing will all help to simplify this process.