While there is a growing volume of evidence suggesting that relatively prevalent functional polymorphisms present within apoptosis-related genes may influence human prostate cancer (PCa) susceptibility, the clinical relevance of these findings remains inconclusive.

Pancreatic cancer is one of the deadliest malignant tumours worldwide. Despite the developments in the treatments of pancreatic cancer, survival rates remain at a low level, and the mechanisms underlying the aggressive course of the cancer are not fully understood. VISTA is an immune checkpoint and has recently become a significant target in cancer treatment; however, the roles of VISTA in the development of pancreatic cancer have largely remained unknown. Histone deacetylase inhibitors (HDACi) have been reported to reverse the epithelial-mesenchymal transition (EMT) and may enhance the efficacy of anti-PD-1 therapy. The PD-L1/PD-1 immune checkpoint targeted by this therapy shares structural similarity with VISTA. Moreover, combination therapy of vorinostat and anti-PD-1 has been shown to significantly reduce tumour growth by suppressing the transcription factor c-Myc. Therefore, in this study, we aim to investigate the genes that are associated with EMT and explore the potential mechanism involving Twist1, a proto-oncogene, and VISTA in pancreatic cancer. We also sought to determine the synergistic effects of an HDACi, vorinostat, in combination with Twist1-siRNA on VISTA expression in pancreatic cancer cells' viability and proliferation. Our results revealed that Twist1 blockade in combination with vorinostat in pancreatic cancer cells suppresses EMT-associated genes and the immune checkpoint VISTA compared to treatments administered alone. As a result, identifying the genes associated with EMT in pancreatic cancer and understanding the role of Twist1 in this process is a crucial step to contribute to the identification of new targets for pancreatic cancer treatment and the improvement of existing treatment strategies.

Mongolia has the highest incidence of liver cancer worldwide, largely driven by a high prevalence of hepatitis virus infections. Mutations in oncogenes and tumor suppressor genes provide valuable insights into the molecular mechanisms of hepatocellular carcinoma (HCC).

Exosomes are extracellular vesicles ranging from 40 to 100 nm in diameter that mediate intercellular communication by transferring proteins, lipids, nucleic acids, and other metabolites. In the context of cancer, exosomes influence the tumor microenvironment by carrying regulatory RNAs such as miRNA, circRNA, and lncRNA. They originate from various cells, including adipocytes, fibroblasts, and hepatocellular carcinoma (HCC) cells, and can either promote or inhibit cancer progression through pathways like MAPK and PI3K-Akt.

Chemotherapy and androgen-deprivation treatment are the curative approaches utilized to suppress prostate cancer (PCa) progression. However, drug resistance and metastasis are extensive and hard to overcome even though remarkable progress has been made in recent decades. The cancer stem cell-related theoretical model explains the distinct molecular characteristics of cancer, its relapse, metastasis, and drug resistance. Meanwhile, noncoding RNA functions in the formation of drug resistance and metastasis in most cancers. The long intergenic nonprotein coding RNA 908 (LINC00908) has been reported to restrain cell proliferation, migration, and invasion of some cancers like triple-negative breast cancer, diffuse large B-cell lymphoma, PCa, and so on. However, its role in stemness for PCa remains unclear.

Existing knowledge regarding the involvement of lncRNA OIP5-AS1 in lung adenocarcinoma (LUAD) development is still incomplete and requires further investigation. Our research aimed to reveal the function of OIP5-AS1 in LUAD. We evaluated the level of OIP5-AS1 and its association with clinicopathological factors in LUAD. The research examined the potential implications of targeting OIP5-AS1 in mitigating the invasive properties of lung cancer cells. A nude mouse xenograft model was utilised to examine tumour growth. We used bioinformatics data and a dual-luciferase reporter assay to study the interactions between OIP5-AS1 and hsa-miR-29b-3p. OIP5-AS1 was significantly overexpressed in LUAD, with a higher level correlating with adverse clinicopathological features. Knockdown of OIP5-AS1 resulted in notable decreases in LUAD cell growth, movement, and aggressive behaviour, accompanied by a decrease in tumour size in vivo. Furthermore, OIP5-AS1 was confirmed to act as a molecular sponge for hsa-miR-29b-3p. The elevated expression of hsa-miR-29b-3p intensified the inhibitory outcomes of OIP5-AS1 knockdown on LUAD cell properties. ZIC5 was experimentally determined to be a direct molecular target of hs-miR-29b-3p, emphasising its integral position in the regulatory interaction. This study reveals a new regulatory route involving OIP5-AS1, hsa-miR-29b-3p and ZIC5 in LUAD pathogenesis. Given its oncogenic traits, OIP5-AS1 presents a promising predictive biomarker and therapeutic target for optimising lung cancer treatment.

Dysregulation of deubiquitination is essential for cancer growth. However, the role of 26S proteasome non-ATPase regulatory subunit 14 (PSMD14) in the progression of triple-negative breast cancer (TNBC) remains to be determined. Gain- and loss-of-function experiments showed that silencing PSMD14 notably attenuated the growth, invasion, and metastasis of TNBC cells in vitro and in vivo. Overexpression of PSMD14 produced the opposite results. Mechanistically, PSMD14 decreased K63-linked ubiquitination on SF3B4 protein to de-ubiquitin and stabilize SF3B4 protein. Then, SF3B4/HNRNPC complex bound to FADS1 mRNA and promoted exon inclusion in the target mRNA through m6A site on FADS1 mRNA recognized by HNRNPC, thereby up-regulating the expression of FADS1 and activating Akt/mTOR signaling. Exogenous arachidonic acid supplementation combined with PSMD14 knockdown induced synthetic lethality, which was further confirmed in TNBC organoid (PDO) and TNBC patient-derived xenograft (PDX) mouse models. Overall, our findings reveal an oncogenic role of PSMD14 in TNBC progression, which indicates a potential biomarker and ferroptosis-mediated therapeutic strategy for TNBC.

MicroRNAs (miRNAs) are emerging as circulating biomarkers in germ cell tumors (GCT) with potential to guide management. Their role and expression patterns are more established in testicular GCTs, while lesser data exist in ovarian GCTs (OGCT).

Non-coding RNAs (ncRNAs) are functional RNA molecules that do not code for proteins. Among these, circular RNAs (circRNAs) represent a recently identified class of endogenous ncRNAs with a pivotal role in gene regulation, alongside short ncRNAs (e.g., microRNAs or miRNAs) and long non-coding RNAs (lncRNAs). CircRNAs are characterized by their single-stranded, covalently closed circular structure, which lacks polyadenylated tails and 5'-3' ends. This unique circular conformation makes them resistant to exonuclease degradation, rendering them more stable than linear RNAs, such as mRNAs in human blood cells, which highlights their potential as biomarkers. Both linear and circular RNAs are derived from pre-mRNA precursors. However, while linear RNAs are produced through conventional splicing, circRNAs are primarily formed through a process known as reverse splicing. CircRNAs can be categorized into five basic types: exon circRNAs, circular intronic RNAs, exon-intron circRNAs, intergenic circRNAs, and fusion circRNAs. These molecules have been shown to significantly influence key hallmarks of cancer, including sustained growth signaling, proliferation, angiogenesis, resistance to apoptosis, unlimited replicative potential, and metastasis. This article will delve into the biogenesis and functions of circRNAs, explore their roles in cancer, and discuss their potential applications as therapeutic options and diagnostic biomarkers.

Recent studies have revealed that CD8+ T cells can be activated via genetic upregulation of HIF-1α, thereby augmenting antitumor effector functions. HIF-1α upregulation can be attained by inhibiting HIF-prolyl hydroxylase (HIF-PH) under normoxic conditions, termed pseudohypoxia. This study investigated whether pseudohypoxia induced by HIF-PH inhibitors suppresses Microsatellite stable (MSS) colorectal cancer (CRC) by affecting tumor immune response.

While neoadjuvant chemotherapy combined with surgical resection has improved the prognosis for patients with osteosarcoma, its impact on metastatic and recurrent cases remains limited. Immunotherapy is emerging as a promising alternative. However, the relationship between the phenotype of tumor-associated macrophages and the prognosis of osteosarcoma remains unclear. Differentially expressed gene during macrophage polarization were identified using the Monocle package. Weighted gene co-expression network analysis was conducted to select genes regulating macrophage polarization. The least absolute shrinkage and selection operator algorithm and multivariate Cox regression were used to construct long-term survival predictive strategies. Multiple machine learning algorithms identified target genes for pan-cancer analysis. Lentiviral transfection created stable strains with target gene knockdown, and CCK-8 and transwell migration assays verified the target gene's effects. Western blot and flow cytometry assessed the impact of target genes on macrophage polarization. A total of 141 genes regulating macrophage polarization were identified, from which eight genes were selected to construct prognostic models. Significant differences between high-risk and low-risk groups were observed in immune cell activation, immune-related signaling pathways, and immune function. The prognostic model and target gene were validated to provide more precise immunotherapy options for osteosarcoma and other tumors. BNIP3 knockdown decreased osteosarcoma cell proliferation and migration and promoted macrophage polarization to the M2 phenotype. The constructed prognostic model offers precise immunotherapy regimens and valuable insights into mechanisms underlying current studies. Furthermore, BNIP3 may serve as a potential immunotherapeutic target for osteosarcoma and other tumors.

Androgen receptor (AR), a member of the nuclear receptor superfamily controls prostate epithelial cell plasticity by repressing a panel of genes involved in epithelial-mesenchymal transition (EMT), including the human CDH2 gene encoding N-cadherin. At the opposite, pathological AR variants such as AR-V7 associated with prostate tumor progression upregulate those EMT genes. Here, focusing on the human CDH2 gene, we show that this duality between AR and AR-V7 relies on a potential human accelerated region present in the intron 1. This fastest-evolving region of the human genome is actually a variable number tandem repeat (VNTR) comprising 24 repetitions of a DNA sequence that englobes binding sites for steroid hormone receptors, recombination signal binding protein for immunoglobulin kappa j region (RBPJ) an effector of the Notch pathway, and zinc finger e-box binding homeobox 1 (ZEB1). Genomic DNA sequencing, multiple sequence alignment, data mining, as well as protein-DNA interaction and gene expression analyses indicate that this VNTR constitutes a potential transcriptional hub for different transcription factors to control human CDH2 expression. Also, our data suggest that prostate tumor cells may unlock an up to now unknown molecular mechanism associated with a fine-tuned control of human CDH2 gene expression.

To investigate the apoptotic and anti-angiogenic effects of metformin in human MCF7 breast cancer cells.

Lung cancer is one of the most lethal types of cancer, and effective diagnostic biomarkers are required. There is increasing evidences that exosome-secreted lncRNAs could play an important role in lung cancer diagnosis. However, the diagnostic value and molecular mechanism of the key lncRNA PITPNA-AS1 in lung cancer remain unclear.

For centuries, a competitive evolutionary race between prokaryotes and related phages or other mobile genetic elements has led to the diversification of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) and CRISPR‑associated sequence (Cas) genome‑editing systems. Among the different CRISPR/Cas systems, the CRISPR/Cas9 system has been widely studied for its precise DNA manipulation; however, due to certain limitations of direct DNA targeting, off‑target effects and delivery challenges, researchers are looking to perform transient knockdown of gene expression by targeting RNA. In this context, the more recently discovered type VI CRISPR/Cas13 system, a programmable single‑subunit RNA‑guided endonuclease system that has the capacity to target and edit any RNA sequence of interest, has emerged as a powerful platform to modulate gene expression outcomes. All the Cas13 effectors known so far possess two distinct ribonuclease activities. Pre‑CRISPR RNA processing is performed by one RNase activity, whereas the two higher eukaryotes and prokaryotes nucleotide‑binding domains provide the other RNase activity required for target RNA degradation. Recent innovative applications of the type VI CRISPR/Cas13 system in nucleic acid detection, viral interference, transcriptome engineering and RNA imaging hold great promise for disease management. This genome editing system can also be employed by the Specific High Sensitivity Enzymatic Reporter Unlocking platform to identify any tumor DNA. The discovery of this system has added a new dimension to targeting, tracking and editing circulating microRNA/RNA/DNA/cancer proteins for the management of cancer. However, there is still a lack of thorough understanding of the mechanisms underlying some of their functions. The present review summarizes the recent updates on the type VI CRISPR/Cas system in terms of its structural and mechanistic properties and some novel applications of this genome‑editing tool in cancer management. However, some issues, such as collateral degradation of bystander RNA, impose major limitations on its in vivo application. Furthermore, additional challenges and future prospects for this genome editing system are described in the present review.

Colorectal cancer (CRC) is a leading health issue and treatments to eradicate it, such as conventional chemotherapy, are non‑selective and come with a number of complications. The present review focuses on the relatively new area of precision oncolytic viral therapy (OVT), with genetic targeting and immune modifications that offer a new future for CRC treatment. In the present review, an overview of the selection factors that are considered optimal for an oncolytic virus, mechanisms of oncolysis and immunomodulation applied to the OVT, as well as new strategies to improve the efficacy of this method are described. Additionally, cause‑and‑effect relationships are examined for OVT efficacy, mediated by the tumor microenvironment, and directions for genetic manipulation of viral specificity are explored. The possibility of synergy between OVT and immune checkpoint inhibitors and other treatment approaches are demonstrated. Incorporating the details of the present review, biomarker‑guided combination therapies in precision OVT for individualized CRC care, significant issues and future trends in this required area of medicine are highlighted. Increasingly, OVT is leaving the experimental stage and may become routine practice; it provides a new perspective on overcoming CRC and highlights the importance of further research and clinical work.

Colorectal cancer (CRC), the third most prevalent cancer globally, shows a diminished 5‑year survival rate compared with patients at early stages of the disease, underscoring the urgency for early diagnostic biomarker identification. The C‑X‑C motif chemokine ligand (CXCL) family plays a significant role in immune modulation and cancer progression. the present study constructed a prognostic model for CXCL family in CRC and conducted an in‑depth investigation of the hub gene CXCL9 within the model. CXCL9 is highly expressed in CRC while high expression levels of CXCL9 in patients with CRC often indicates an improved prognosis. Through Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and gene set enrichment analysis enrichment analysis, it was discovered that CXCL9 is not only associated with immune modulation but also closely related to pathways that affect the occurrence and development of cancer. CXCL9 is closely related to mitophagy and blocks autophagy flow by altering the expression of autophagy‑related genes. Additionally, it was found that CXCL9 is a downstream gene modified by ALKBH5 and can partially restore the tumor‑suppressive effects induced by the knockdown of ALKBH5. These studies indicated that CXCL9 is a prognostic marker in CRC and plays a dual role in cancer progression: It activates immune responses on one hand and promotes the malignant characteristics of cancer on the other hand.

Tumor-infiltrating CD8+ T cells are critical for anti-tumor immunity and positively associated with patient survival. However, the mechanisms governing CD8+ T cell infiltration remain incompletely elucidated, particularly those involving circular RNAs (circRNAs). In this study, we characterized circRNA expression profiles in four paired normal and tumor tissues of non-small-cell lung cancer (NSCLC) and identified that circFNDC3B, a circular transcript derived from exons 2 and 3 of the fibronectin type III domain containing 3B (FNDC3B) gene, as significantly upregulated in NSCLC tissues. Mechanistic investigations revealed that circFNDC3B directly binds to transcription factor II-I (TFII-I), forming an RNA-protein complex that competitively disrupts the interaction between TFII-I and STAT1. This sequestration abrogates the transcriptional activation of CXCL10 and CXCL11, two critical chemokines governing CD8+ T cell chemoattraction. Consequently, reduced CXCL10/11 expression significantly impairs CD8+ T cell infiltration into the tumor microenvironment. Consistently, the murine ortholog circFndc3b expression exhibits an inverse correlation with CD8+ T cell infiltration in tumors. Our study uncovers a crucial circRNA-mediated regulatory axis wherein circFNDC3B impedes anti-tumor immunity by suppressing chemokine-dependent CD8+ T cell recruitment, positioning circFNDC3B as a potential therapeutic target to enhance CD8+ T cell-mediated anti-tumor responses in NSCLC.

Analysing the genome, epigenome, transcriptome, proteome, and metabolome within the spatial context of cells has transformed our understanding of tumour spatiotemporal heterogeneity. Advances in spatial multi-omics technologies now reveal complex molecular interactions shaping cellular behaviour and tissue dynamics. This review highlights key technologies and computational methods that have advanced spatial domain identification and their pseudo-relations, as well as inference of intra- and inter-cellular molecular networks that drive disease progression. We also discuss strategies to address major challenges, including data sparsity, high-dimensionality, scalability, and heterogeneity. Furthermore, we outline how spatial multi-omics enables novel insights into disease mechanisms, advancing precision medicine and informing targeted therapies. KEY POINTS: Advancements in spatial multi-omics facilitate our understanding of tumour spatiotemporal heterogeneity. AI-driven multimodal models uncover complex molecular interactions that underlie cellular behaviours and tissue dynamics. Combining multi-omics technologies and AI-enabled bioinformatics tools helps predict critical disease stages, such as pre-cancer, advancing precision medicine, and informing targeted therapeutic strategies.

Hepatocellular carcinoma remains one of the most lethal cancers, characterized by poor prognosis and low life expectancy. Unfortunately, there are very few molecular therapeutic options available for it. Sorafenib is a current standard first-line treatment for advanced hepatocellular carcinoma, however, drug resistance significantly limits its therapeutic efficacy.