Mutations in the RAS gene family (NRAS, KRAS) are critical drivers of late-stage acute myeloid leukemia (AML) progression. They are frequently detected in relapsed/refractory AML and AML transformed from myelodysplastic syndrome (MDS). Occurring as late-stage genetic events, RAS mutations synergize with early drivers to promote leukemogenesis. While mutually exclusive with FLT3-ITD mutations, they coexist with KIT, RUNX1, CEBPA mutations and MLL rearrangements. Granulocyte-monocyte progenitors (GMPs) serve as the cellular origin for RAS-mutant leukemia stem cells (LSCs). Ultimately, RAS mutations drive monocytic differentiation of LSCs and venetoclax (VEN) resistance through BCL-2 family rewiring. Beyond AML, they are hallmark genetic lesions in juvenile myelomonocytic leukemia (JMML) and present in 15%-20% of pediatric acute lymphoblastic leukemia (ALL) cases. Here, we propose a comprehensive pathogenic model and targeted therapeutic framework focusing on RAS, MCL-1, BCL2L1 to overcome drug resistance and improve patient outcomes.

Acute myeloid leukemia (AML) remains a highly lethal hematologic malignancy characterized by metabolic reprogramming, therapeutic resistance, and poor survival, particularly in older patients. Nicotinamide adenine dinucleotide (NAD⁺) metabolism has emerged as a central driver of AML progression, and recent studies have identified solute carrier family 25 member 51 (SLC25A51) as the primary mitochondrial NAD⁺ transporter in mammalian cells. SLC25A51 regulates mitochondrial redox balance, oxidative phosphorylation, and tricarboxylic acid (TCA) cycle activity, thereby sustaining leukemic proliferation and survival. Structural studies have elucidated its six-transmembrane helix architecture, salt-bridge-mediated transport mechanism, and stabilization by cardiolipin binding. Functional investigations demonstrate that SLC25A51 overexpression correlates with poor prognosis, while its depletion disrupts mitochondrial metabolism, induces apoptosis, and suppresses AML progression in vivo. Therapeutically, pharmacologic inhibition of SLC25A51 with fludarabine, or its combination with hypomethylating agents, such as 5-azacytidine, enhances antileukemic efficacy by perturbing metabolic and epigenetic regulation. Moreover, SLC25A51 expression may serve as a predictive biomarker for mitochondrial-targeted therapies, such as complex I inhibitors. Future translational research should focus on developing selective inhibitors, optimizing combination strategies with demethylating agents and BCL-2 inhibitors, and validating its prognostic significance in clinical cohorts. Collectively, SLC25A51 represents a promising metabolic target with potential to overcome therapeutic resistance and improve patient outcomes in AML. Furthermore, this review discusses its potential implications across distinct genetic subtypes of AML (e.g., mutations in TP53, NPM1, and RAS), thereby highlighting key directions for future translational research.

Purpose:Colorectal cancer (CRC) remains a leading cause of cancer-related mortality worldwide. Actinidia chinensis Planch Root extracts (acRoots), a traditional Chinese medicine (TCM), possess recognized anticancer properties, but their efficacy and mechanism in Colorectal cancer are not fully understood. This study investigates the role of acRoots in suppressing Colorectal cancer progression, with a specific focus on its potential to induce ferroptosis, a form of iron-dependent cell death. Methods:The anti-tumor effects of acRoots were evaluated in human Colorectal cancer cell lines (HCT-15, CW-2) using Cell Counting Kit-8 (CCK-8), colony formation, wound healing, and Transwell assays. Cell death was analyzed by Annexin V-FITC/PI flow cytometry. Mechanisms were probed by measuring reactive oxygen species (ROS), glutathione (GSH) levels, malondialdehyde (MDA) levels, and performing qRT-PCR and Western blot for ferroptosis-related markers (SLC7A11, GPX4, p53). The ferroptosis inhibitor Ferrostatin-1 (Fer-1) was used in rescue experiments. The in vivo antitumor efficacy was assessed in HCT-15 xenograft models in nude mice treated orally with acRoots (150 mg/kg/day) for 14 days. Results:The acRoots significantly and dose-dependently inhibits the viability, proliferation, migration, and invasion of colorectal cancer cells. Concurrently, acRoots effectively induces ferroptosis in these cells, characterized by intracellular reactive oxygen species (ROS) accumulation, glutathione (GSH) depletion, and a significant increase in the lipid peroxidation product malondialdehyde (MDA). These ferroptosis-related phenotypes can be reversed by the ferroptosis-specific inhibitor Ferrostatin-1 (Fer-1). Mechanistically, acRoots upregulates the expression of the tumor suppressor gene p53, subsequently downregulating the expression levels of key ferroptosis regulators SLC7A11 and GPX4. Furthermore, pretreatment with Fer-1 effectively reverses acRoots-induced cytotoxicity and ROS accumulation. In an HCT-15 xenograft mouse model, oral administration of acRoots (150 mg/kg/day) significantly inhibited tumor growth, reduced intratumoral GSH levels, and no obvious toxicity was observed. Conclusion:Our findings demonstrate that acRoots exerts potent anti-Colorectal cancer effects by inhibiting malignant phenotypes and inducing ferroptosis. This ferroptosis is mediated, at least in part, through the p53-dependent downregulation of the SLC7A11/GPX4 axis. These results position acRoots as a promising therapeutic candidate and a novel natural ferroptosis inducer for Colorectal cancer treatment, warranting further clinical investigation.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is widely regarded as the most potent curative cell therapy for a range of malignancies, particularly hematologic cancers. However, its clinical application remains significantly constrained by acute graft-versus-host disease (aGVHD), a severe and potentially fatal complication. As such, developing more effective strategies to prevent and manage aGVHD has become an urgent priority in the field. In a groundbreaking study, the team led by Zhan Cheng and Zhu Xiaoyu introduced a novel time-based approach, revealing that the biological rhythm regulating the immune microenvironment can be harnessed to optimize the timing of hematopoietic stem cell infusion. Their findings demonstrate that this chronotherapeutic strategy can significantly reduce the incidence of aGVHD, offering a simple, drug-free, and cost-free innovation to improve outcomes in allo-HSCT.

Voltage-dependent anion channel 2 (VDAC2) is a pivotal β-barrel protein located in the mitochondrial outer membrane (MOM), playing a central role in metabolite transport, ion homeostasis, and the determination of cell fate. Compared to other isoforms in the same family, VDAC2 possesses unique structural features—including an N-terminal extension, an enrichment of cysteine residues, and a distinct β-barrel conformation—which underlie its non-redundant functional roles. Notably, VDAC2 acts as a “dual regulatory hub” in apoptosis: it suppresses apoptosis by directly binding and inhibiting BAK, while also being essential for BAX-mediated apoptosis, demonstrating marked context-dependency. Furthermore, VDAC2 is deeply involved in tumor progression through its regulation of metabolic reprogramming, reactive oxygen species (ROS) homeostasis, ferroptosis, and mitochondrial quality control. Dysregulation of VDAC2 expression is closely associated with prognosis in multiple cancers, highlighting its promise as a diagnostic and prognostic biomarker, as well as a therapeutic target. This review systematically consolidates current knowledge on VDAC2 in oncology, identifies limitations and challenges in existing research, and aims to offer strategic insights to guide future investigations.

Acute promyelocytic leukemia (APL) is a rare and aggressive subtype of acute myelogenous leukemia (AML), characterized by the PML-RARA fusion gene. When APL presents concurrently with acquired immunodeficiency syndrome (AIDS), it creates unique challenges in diagnosis and treatment due to the immunocompromised state of the patient. This case report describes a 46-year-old male patient with long-standing AIDS who developed APL. Initial treatment involved all-trans retinoic acid (ATRA) monotherapy due to the patient’s severe lung infection and liver dysfunction, followed by the addition of arsenic trioxide (ATO) once infection and liver function improved. The patient achieved complete remission (CR) after combined ATRA and ATO therapy, with successful molecular remission of the PML-RARA fusion gene. We discuss the complexity of managing APL in the context of HIV infection, including the challenges posed by infections, liver dysfunction, and the impact of chemotherapy on antiretroviral therapy (ART). This case highlights the need for immediate initiation of ATRA in APL patients, even before genetic confirmation, and the potential therapeutic role of ATO in both leukemia treatment and HIV reservoir management. Further studies are needed to optimize treatment protocols for patients with concurrent AIDS and APL, focusing on personalized approaches to maximize efficacy while minimizing complications.

The tumor microenvironment (TME) is an intricate system comprised of tumor cells and the surrounding cellular and non-cellular components, exerting a pivotal influence on the initiation and progression of tumors. Exhibiting dynamic and diverse compositions as well as functional states across various tumors and patients, a profound comprehension of its specific internal interactions is indispensable for formulating efficacious anti-cancer treatment strategies. Extensive interactions among various immune cell types within the TME are well-documented, with their phenotypes and abundances closely linked to clinical prognoses. TME research is progressing towards greater complexity and precision, yet, to date, no representative TME biomarkers suitable for clinical applications have been definitively identified and validated. In a recent study, the collaborative actions of CXCL9 and SPP1 (CXCL9:SPP1) were found to collectively dictate the polarity of tumor-associated macrophages (TAMs) within the TME, exerting profound effects on tumor progression and treatment responses. The mutually exclusive expression of CXCL9:SPP1 in the TME not only governs TAM polarity but also exhibits strong correlations with immune cell profiles, antitumor factors, and patient outcomes, significantly influencing prognosis. This article consolidates the significance and prospects of CXCL9:SPP1 as a novel indicator for tumor development and prognosis, while also proposing future research directions and addressing potential challenges in this promising field.

Cancer arises from genetic alterations that impact both the genome and transcriptome. The utilization of nanopore sequencing offers a powerful means of detecting these alterations due to its unique capacity for long single-molecule sequencing. In the context of DNA analysis, nanopore sequencing excels in identifying structural variations (SVs), copy number variations (CNVs), gene fusions within SVs, and mutations in specific genes, including those involving DNA modifications and DNA adducts. In the field of RNA research, nanopore sequencing proves invaluable in discerning differentially expressed transcripts, uncovering novel elements linked to transcriptional regulation, and identifying alternative splicing events and RNA modifications at the single-molecule level. Furthermore, nanopore sequencing extends its reach to detecting microorganisms, encompassing bacteria and viruses, that are intricately associated with tumorigenesis and the development of cancer. Consequently, the application prospects of nanopore sequencing in tumor diagnosis and personalized treatment are expansive, encompassing tasks such as tumor identification and classification, the tailoring of treatment strategies, and the screening of prospective patients. In essence, this technology stands poised to unearth novel mechanisms underlying tumorigenesis while providing dependable support for the diagnosis and treatment of cancer.

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression. Among these, miR-660, located on chromosome Xp11.23, is increasingly studied for its role in cancer due to its abnormal expression in various biological contexts. It is regulated by 8 competing endogenous RNAs (ceRNAs), which adds complexity to its function. miR- 660 targets 19 genes involved in 6 pathways such as PI3K/AKT/mTOR, STAT3, Wnt/β-catenin, p53, NF‑κB, and RAS, influencing cell cycle, proliferation, apoptosis, and invasion/migration. It also plays a role in resistance to chemotherapies like cisplatin, gemcitabine, and sorafenib in lung adenocarcinoma (LUAD), pancreatic ductal adenocarcinoma (PDAC), and hepatocellular carcinoma (HCC), thus highlighting its clinical importance. Additionally, leveraging liposomes as nanocarriers presents a promising avenue for enhancing cancer drug delivery. Our comprehensive study not only elucidates the aberrant expression patterns, biological functions, and regulatory networks of miR-660 and its ceRNAs but also delves into the intricate signaling pathways implicated. We envisage that our findings will furnish a robust framework and serve as a seminal reference for future investigations of miR-660, fostering advancements in cancer research and potentially catalyzing breakthroughs in cancer diagnosis and treatment paradigms.

Extracellular vesicles (EVs) are emerging as powerful biomarkers in liquid biopsy, offering insights into early cancer diagnosis, precision treatment, and prognosis evaluation. EVs, including microvesicles, exosomes, and apoptotic bodies, carry molecular cargo that reflects the physiological or pathological state of parent cells. Recent research, including findings presented at the 2024 European Society for Medical Oncology (ESMO) meeting, highlights significant advances in using EVs for early detection and prognosis in some solid tumors. While applications hold great potential, challenges remain, including the need for advanced technologies for efficient EV separation and purification, characterizing heterogeneity, detecting single EV markers, and overcoming small sample sizes. Addressing these issues will require increased technical investment, collaborative efforts, and large-scale clinical trials. These steps are essential to overcome the current limitations and to promote the application and development of EV-based approaches in cancer diagnosis and treatment.

As a pivotal microRNA (miRNA), miR-4284 exhibits noteworthy aberrant expression levels across various cancers and diseases, exerting a crucial role in modulating cancer progression and prognosis. This article endeavors to comprehensively elucidate the regulatory mechanisms of miR-4284 in cancer, delving deeply into its impact on tumor cell proliferation, invasion, and metastasis by intervening in key signaling pathways such as p65, mitogen-activated protein kinase (MAPK), and transforming growth factor-β (TGF-β). Moreover, this article examines the potential associations of miR-4284 with diverse current therapeutic strategies, such as cancer prediction models, synergistic effects of chemotherapeutic agents, mechanisms of ultrasound-targeted microbubble destruction technology, and enhancement of radiotherapy. However, despite the significant strides made in miR-4284 research, certain limitations persist. Looking ahead, we anticipate that larger-scale and more in-depth studies will further unveil the functional mechanisms of miR-4284 and elucidate its role in therapeutic drug efficacy, thus furnishing robust theoretical underpinnings for the clinical application of miR-4284.

Approximately 75% of the human genome is transcribed into RNA, yet less than 5% encodes proteins, with the majority producing non-coding RNAs (ncRNAs). Among them, long non-coding RNAs (lncRNAs) represent a major class that exerts broad regulatory influence across cellular processes, disease contexts, and developmental stages. Despite their potential as biomarkers and therapeutic targets, their low sequence conservation, limited abundance, and structural complexity present significant challenges for functional characterization. Traditional RNA interference and CRISPR-Cas9-based methods have offered partial insights but remain limited in efficiency, specificity, and scalability. To address these barriers, Neville E. Sanjana's team developed CaRPool-seq, a transcriptome-scale CRISPR-Cas13 screening platform that directly targets RNA. Applying this approach across diverse human cell lines, they identified 778 essential lncRNAs, including 46 universally required for survival, with distinctive structural features and functional independence from neighboring protein-coding genes. Integration with single-cell transcriptomics revealed their critical roles in cell-cycle regulation, apoptosis, and developmental gene expression, as well as aberrant expression patterns in cancer linked to patient outcomes. This study establishes CRISPR-Cas13 as a precise and scalable strategy for lncRNA functional discovery, expanding opportunities for biomarker identification, therapeutic development, and precision medicine.

tRNA-derived fragments (tRFs) are a newly recognized class of small noncoding RNAs (sncRNAs) that play significant roles in various diseases. The Wnt pathway plays a key role in various physiological processes such as embryonic development, tissue renewal and regeneration. In the regulation of Wnt/β-catenin, Forkhead box k1(FOXK1), Frizzled class receptor 3 (FZD3), and Wnt5b can be targeted and inhibited by three tRFs: tRF3008A targets FOXK1 to inhibit colorectal cancer (CRC), 5'-tiRNAVal targets FZD3 to inhibit breast cancer (BrC), and tRF-22-8BWS7K092 targets Wnt5b to induce ferroptosis in lung cells. Additionally, tRF-24-V29K9UV3IU can inhibit the levels of FZD3, Van Gogh-like protein 1 (VANGL1), and cyclin D2 (CCND2) through an unexplained mechanism and play a role in inhibiting gastric cancer (GC). Clinical data has shown that the expression levels of certain tRFs are associated with the prognosis and pathological features of CRC and BrC patients. Low expression of tRF3008A is associated with poor prognosis and adverse pathological features in CRC patients, while high expression of tiRNA-Phe-GAA-003 and low expression of 5'-tiRNAVal are associated with poor prognosis and adverse pathological features in BrC patients. KEGG analysis has also shown that a variety of tRFs are involved in regulating the Wnt pathway and have been shown to play a role in a variety of diseases. For example, high expression of tRF-Gly-CCC-039 is associated with poor healing of diabetic foot, low expression of tsRNA-10277 is associated with high incidence of steroid-induced osteonecrosis of the femoral head (SONFH), high expression of tRF-22-8BWS7K092 is correlated with the severity of acute lung injury (ALI), and low expression of tsRNA-21109 is associated with the severity of systemic lupus erythematosus (SLE), and high expression of tRF-36-F900BY4D-84KRIME and tRF-23-87R8WP9IY, as well as low expression of tRF-40-86J8WPMN1E8Y7Z2R, were associated with high incidence of varicose vein (VV), and high expression of ts-34, was associated with high mortality of BrC. This article summarizes the biological function and mechanism of tRFs related to the Wnt pathway in cancer and other diseases, providing a new direction for subsequent translational medical research.

Long non-coding RNAs (lncRNAs) are a diverse class of non-coding transcripts longer than 200 nucleotides that play critical roles in gene regulation and disease progression. Among them, MACC1 antisense RNA 1 (MACC1-AS1), located on chromosome 7p21.1, is transcribed in antisense orientation to the metastasis-associated in colon cancer-1 (MACC1) gene. MACC1-AS1 is significantly overexpressed in ten types of cancers and is associated with poor prognosis and clinical characteristics. MACC1-AS1 is transcriptionally or post-transcriptionally regulated by upstream modulators such as interferon-γ (IFN-γ), polypyrimidine tract-binding protein 1 (PTBP1), Smad2, transforming growth factor-β1 (TGF-β1), and Kras. In turn, MACC1-AS1 influences downstream effectors through three principal molecular mechanisms: acting as a competitive endogenous RNA (ceRNA) to modulate the microRNA (miRNA)-mRNA axis, binding antisense to MACC1 mRNA, and regulating transcription factors as well as downstream protein expression. MACC1-AS1 participates in multiple cellular signaling pathways, including AMPK, Hippo, PI3K/AKT, and Notch1 pathways. MACC1-AS1 modulates proliferation, apoptosis, epithelial-mesenchymal transition (EMT), invasion, migration, and the maintenance of cancer stemness. Moreover, MACC1-AS1 contributes to therapeutic resistance, conferring reduced sensitivity to chemotherapeutic agents such as 5-fluorouracil (5-FU), oxaliplatin, gemcitabine, and cisplatin, as well as to combination regimens including 5-fluorouracil and oxaliplatin (FOLFOX). This review provides an overview of the current knowledge surrounding MACC1-AS1 and highlights its potential as both a biomarker and a therapeutic target for future translational research.

MicroRNAs (miRNAs), a distinctive class of small single-stranded non-coding RNA molecules typically spanning between 21 and 23 nucleotides, hold a pivotal position within the intricate regulatory network governing gene expression. Notably, miR-767, located on chromosome Xq28, has emerged as a significant player in tumor development, with its two mature products, miR-767-3p and miR-767-5p, garnering considerable attention in scientific inquiry. Extensive investigations reveal aberrant expression patterns of miR-767 across a spectrum of cancers affecting neurological, digestive, reproductive, urinary, and respiratory systems. Remarkably, miR-767 exhibits substantial upregulation in 13 distinct cancer types and demonstrates precise targeting of at least 14 pivotal protein-coding genes (PCGs) crucial for regulating cellular processes including the cell cycle, proliferation, epithelial-mesenchymal transition (EMT), invasion, and migration. Moreover, the expression level of miR-767 bears significant implications for cancer patient diagnosis, prognosis, and drug sensitivity, thus offering novel insights for clinical tumor management. At the mechanistic level, miR-767-5p and miR-767-3p intricately participate in the regulation of key signaling pathways, with miR-767-5p influencing JAK/STAT, EPK1/2, and PI3K/Akt pathways, while miR-767-3p predominantly affects TGF-β and PI3K/Akt pathways. Notably, both miRNAs converge on the PI3K/Akt pathway, underscoring its pivotal role in their joint regulation. This review provides a comprehensive analysis of the intricate mechanisms underlying miR-767-mediated tumor progression through the modulation of diverse target genes, and explores the potential correlation between host gene GABRA3 transcription and the expression of these miRNAs. Furthermore, the review systematically delineates the binding sites of miR-767-5p and miR-767-3p with circRNA and target genes, alongside the PCGs regulated by miR-767, offering profound insights into their multifaceted roles in tumor development. In essence, this review not only comprehensively elucidates the pivotal role of miR-767 in tumor progression but also provides valuable cues and avenues for future research, thereby fostering deeper scientific inquiry within the realm of cancer research.