The balance of programmed cell death (PCD) mechanisms, including apoptosis, autophagy, necroptosis and others, is pivotal in cancer progression and treatment. Dysregulation of these pathways results in uncontrolled cell growth and resistance to conventional therapies. Nanomedicine offers a promising solution in oncology through targeted drug delivery enabling precise targeting of cancer cells while preserving healthy tissues. This approach reduces the side effects of traditional chemotherapy and enhances treatment efficacy by engaging PCD pathways. We details each PCD pathway, their mechanisms, and innovative nanomedicine strategies to activate these pathways, thereby enhancing therapeutic specificity and minimizing harm to healthy tissues. The precision of nanotechnology in targeting PCD pathways promises significant improvements in cancer treatment outcomes. This synergy between nanotechnology and targeted PCD activation could lead to more effective and less toxic cancer therapies, heralding a new era in cancer treatment.

20E (20-Hydroxyecdysone) is a central steroid hormone that orchestrates developmental changes and metamorphosis in arthropods. While its molecular mechanisms have been recognized for some time, detailed elucidation has primarily emerged in the past decade. PCD (Programmed cell death), including apoptosis, necrosis, efferocytosis, pyroptosis, ferroptosis, and autophagy, plays a crucial role in regulated cell elimination, which is vital for cells’ development and tissue homeostasis. This review summarizes recent findings on 20E signaling regulated autophagy and apoptosis in insects, including Drosophila melanogaster, Bombyx mori, Helicoverpa armigera, and other species. Firstly, we comprehensively explore the biosynthesis of the sterol hormone 20E and its subsequent signal transduction in various species. Then, we focus on the involvement of 20E in regulating autophagy and apoptosis, elucidating its roles in both developmental contexts and bacterial infection scenarios. Furthermore, our discussion unfolds as a panoramic exposition, where we delve into the fundamental questions with our findings, anchoring them within the grander scheme of our study in insects. Deepening the understanding of 20E-autophagy/apoptosis axis not only underscores the intricate tapestry of endocrine networks, but also offers fresh perspectives on the adaptive mechanisms that have evolved in the face of environmental challenges.

Autophagy, a crucial cellular mechanism responsible for degradation and recycling of intracellular components, is modulated by an intricate network of molecular signals. Its paradoxical involvement in oncogenesis, acting as both a tumor suppressor and promoter, has been underscored in recent studies. Central to this regulatory network are the epigenetic modifications of DNA and RNA methylation, notably the presence of N6-methyldeoxyadenosine (6mA) in genomic DNA and N6-methyladenosine (m6A) in eukaryotic mRNA. The 6mA modification in genomic DNA adds an extra dimension of epigenetic regulation, potentially impacting the transcriptional dynamics of genes linked to autophagy and, especially, cancer. Conversely, m6A modification, governed by methyltransferases and demethylases, influences mRNA stability, processing, and translation, affecting genes central to autophagic pathways. As we delve deeper into the complexities of autophagy regulation, the importance of these methylation modifications grows more evident. The interplay of 6mA, m6A, and autophagy points to a layered regulatory mechanism, illuminating cellular reactions to a range of conditions. This review delves into the nexus between DNA 6mA and RNA m6A methylation and their influence on autophagy in cancer contexts. By closely examining these epigenetic markers, we underscore their promise as therapeutic avenues, suggesting novel approaches for cancer intervention through autophagy modulation.

Post-translational modifications refer to the chemical alterations of proteins following their biosynthesis, leading to changes in protein properties. These modifications, which encompass acetylation, phosphorylation, methylation, SUMOylation, ubiquitination, and others, are pivotal in a myriad of cellular functions. Macroautophagy, also known as autophagy, is a major degradation of intracellular components to cope with stress conditions and strictly regulated by nutrient depletion, insulin signaling, and energy production in mammals. Intriguingly, in insects, 20-hydroxyecdysone signaling predominantly stimulates the expression of most autophagy-related genes while concurrently inhibiting mTOR activity, thereby initiating autophagy. In this review, we will outline post-translational modification-regulated autophagy in insects, including Bombyx mori and Drosophila melanogaster, in brief. A more profound understanding of the biological significance of post-translational modifications in autophagy machinery not only unveils novel opportunities for autophagy intervention strategies but also illuminates their potential roles in development, cell differentiation, and the process of learning and memory processes in both insects and mammals.

RNA methylation, characterized by modifications such as N⁶-methyladenosine, 5-methylcytosine, and N¹-methyladenosine plays a crucial role in post-transcriptional gene regulation across diverse biological systems. While research on RNA methylation has predominantly focused on mammals, particularly its roles in epigenetic regulation and cancer biology, recent studies in insects have begun to explore their extensive functions in insect physiology. This review examines the mechanisms by which RNA methylation regulates growth, development, reproduction, environmental adaptation, and immune response in insects, providing insights into the biological characteristics of these organisms without prematurely speculating on pest control strategies. It aims to offer valuable insights into the role of RNA methylation in insect biology and resistance.

Breast cancer remains one of the deadliest diseases around the world. This study systematically investigates the expression profile and clinical significance of RIBC2 in breast cancer. By integrating multi-omics data from public databases, such as The Cancer Genome Atlas and The Genotype-Tissue Expression project, combined with bioinformatic analyses and molecular docking simulations, we demonstrated that RIBC2 is significantly overexpressed in breast cancer tissues. Elevated RIBC2 expression was positively correlated with higher T stage, advanced pathological stage, and poorer overall survival. Functional enrichment analyses indicated that RIBC2 may facilitate tumor invasion by regulating extracellular matrix remodeling and activating the mitogen-activated protein kinase signaling pathway. Multivariate Cox regression analysis confirmed high RIBC2 expression as an independent poor prognostic factor, with its inclusion slightly increasing the area under the curve of the prognostic model from 0.762 to 0.764. Moreover, immune infiltration analysis revealed that high RIBC2 expression was associated with increased infiltration of regulatory T cells and M2-polarized macrophages, indicating a potential role in shaping an immune suppressive tumor microenvironment. Spearman correlation analysis between RIBC2 and immune checkpoints showed significant positive associations only for lymphocyte activation gene 3 protein (p<0.001, absolute correlation ≈ 0.1) and human leukocyte antigen-C (p=0.045, absolute correlation ≈ 0.08), indicating RIBC2 may selectively modulate specific immunosuppressive pathways. Drug sensitivity analysis further suggested that RIBC2 overexpression may contribute to chemotherapy resistance. The methylation level of RIBC2 was found to be significantly negatively correlated with its expression, suggesting that hypermethylation in the promoter or regulatory regions may suppress gene expression through epigenetic silencing mechanisms. Furthermore, quantitative polymerase chain reaction revealed a 4.2-fold RIBC2 upregulation in triple-negative breast cancer cells (MDA-MB-231) compared to normal mammary cells (Hs578bst), exceeding levels in luminal subtypes (MCF-7). Collectively, these findings highlight RIBC2 as a promising prognostic biomarker and provide a theoretical foundation for developing combination therapeutic strategies targeting RIBC2.