The crosstalk between the tumour immune microenvironment (TIME) and tumour cells promote immune evasion and resistance to immunotherapy in gastrointestinal (GI) tumours. Post-transcriptional regulation of genes is pivotal to GI tumours progression, and RNA-binding proteins (RBPs) serve as key regulators via their RNA-binding domains. RBPs may exhibit either anti-tumour or pro-tumour functions by influencing the TIME through the modulation of mRNAs and non-coding RNAs expression, as well as post-transcriptional modifications, primarily N6-methyladenosine (m6A). Aberrant regulation of RBPs, such as HuR and YBX1, typically enhances tumour immune escape and impacts prognosis of GI tumour patients. Further, while targeting RBPs offers a promising strategy for improving immunotherapy in GI cancers, the mechanisms by which RBPs regulate the TIME in these tumours remain poorly understood, and the therapeutic application is still in its early stages. This review summarizes current advances in exploring the roles of RBPs in regulating genes expression and their effect on the TIME of GI tumours, then providing theoretical insights for RBP-targeted cancer therapies.

Current miRNA detection methods mainly focus on the detection of discrete targets while overlooking the logical relationship among biomoleculars. Integrating electrochemical sensor, DNA framework probes and DNA logic gate technology for analyzing miRNAs with diverse combinations in bodily fluids provide a potential way for recognition of multiple cancers. In this work, a novel cascaded logic gate-based electrochemical (EC) analysis strategy was designed and fabricated for the discrimination of pancreatic cancer (PC), breast cancer (BC) and lung cancer (LC). Cascaded AND logic gates were constructed through the logical relationship among miR-21, miR-155, miR-373, miR-6746 and miR-1343 which abnormally expressed in PC, BC and LC. The output strands of the logic gates were captured by tetrahedral DNA framework probes modified on the electrodes of EC sensor. Three cascaded AND logic gates successfully achieved limits of detection (LOD) of 0.62 nM, 0.37 nM and 0.41 nM, and good linear relationships between current values and the concentration of miRNA combinations within the range from 1 nM to 1 μM (R2 > 0.99). It was shown that multiple cascaded logic gate-based EC method could distinguish PC, BC and LC through specific miRNA combinations both in a TM buffer and in a 50 % fetal bovine serum samples. This logic gate-based EC method has the advantages of precision, high speed and logical analysis capability which provides a brand-new tool for system and precision medicine.

Non-coding accounts for 98 %-99 % of the human genome and performs many essential regulatory functions in eukaryotes, involved in cancer development and development. Non-coding RNAs are abundantly enriched in exosomes, which play a biological role as vectors. Some biofunctional non-coding RNAs are specifically designed as exosomes for the treatment of cancers such as glioma. Glioma is one of the most common primary tumors within the skull and has varying degrees of malignancy and histologic subtypes of grades I-IV. Gliomas are characterized by high malignancy and an abundant blood supply due to rapid cell proliferation and vascularization, often with a poor prognosis. Exosomal non-coding RNAs can be involved in the tumorigenesis process of glioma from multiple directions, such as angiogenesis, tumor proliferation, metastatic invasion, immune evasion, apoptosis, and autophagy. Therefore, non-coding RNAs in exosomes are suitable as markers or therapeutic targets for early diagnosis of diseases and for predicting the prognosis of a variety of diseases. Regulating exosome production and the level of exosomal non-coding RNA expression may be a new approach to prevent or eliminate glioma. In this review, we review the origin and characteristics of exosomal non-coding RNAs, and introduce the functional studies of exosomal non-coding RNAs in glioma and their potential clinical applications, in order to broaden new ideas for the treatment of glioma.

RNA targeting represents an original and promising approach to the discovery of new therapeutic tools against numerous diseases. The majority of intracellular RNAs are noncoding RNAs that play key regulatory functions in many physiological processes. Among these RNAs, long noncoding RNAs (lncRNAs) constitute the largest class of noncoding transcripts and have been shown to play important functional roles in development and disease processes. In this work, we developed a set of biochemical assays for the discovery of efficient small-molecule lncRNA ligands selective for their target, focusing on MALAT1 lncRNA. The latter bears a particular structure including a triple helical region important for its function, and it has been linked to cancer cells' proliferation. However, its role in cancer still needs to be completely elucidated. The application of these assays to an original library of RNA binders allowed for the discovery of unprecedented ligands of the MALAT1 triple helix able to inhibit and destabilize the triple helical MALAT1 structure. The set of screening and validation assays developed could find application in the discovery of new MALAT1 binders, and the new chemical scaffolds discovered in this study represent promising chemical probes for the study of the biological role of MALAT1 in disease.

Chronic low back pain associated with intervertebral disc degeneration (IVDD) is significantly aggravated in patients with diabetes mellitus (DM); however, the underlying molecular mechanisms remain unclear. This study explored the role of the long non-coding RNA AGEAT (AGE-associated transcript) in the pathogenesis of DM-associated IVDD. Whole-transcriptome sequencing of rat nucleus pulposus cells (NPCs) treated with advanced glycation end products (AGEs) revealed a time-dependent upregulation of AGEAT. AGEAT overexpression induced NPC apoptosis, mitochondrial dysfunction, and extracellular matrix (ECM) degradation. Mechanistically, RNA fluorescence in situ hybridization localized AGEAT to the cytoplasm, where it acted as a competing endogenous RNA (ceRNA) by directly binding miR-204-5p, thereby relieving repression of its target Mapk4. Silencing AGEAT via siRNA significantly reduced apoptosis, restored mitochondrial function, and preserved ECM integrity. In vivo, intra-discal injection of AAV-sh-AGEAT in diabetic IVDD rats significantly improved disc integrity, as evidenced by a reduction in MRI Pfirrmann grade and histological preservation of NPC density and collagen II content. Collectively, these findings establish AGEAT as a key ceRNA that exacerbates diabetic IVDD via the miR-204-5p/Mapk4 axis, promoting NPC apoptosis, mitochondrial dysfunction, and ECM degradation. Targeting this pathway-through AGEAT silencing or miR-204-5p activation-represents a promising therapeutic strategy for mitigating diabetes-associated disc degeneration. This study reveals the critical role of the AGEAT/miR-204-5p/Mapk4 axis in the progression of DM-associated IVDD, suggesting a potential therapeutic strategy for its treatment.

Molecular surface analysis can provide a high-dimensional, rich representation of molecular properties and interactions, which is crucial for enabling powerful predictive modeling and rational molecular design across diverse scientific and technological domains. With remarkable successes achieved by artificial intelligence (AI) in different fields such as computer vision and natural language processing, there is a growing imperative to harness AI's potential in accelerating molecular discovery and innovation. The integration of AI techniques with molecular surface analysis has opened up new frontiers, allowing researchers to uncover hidden patterns, relationships, and design principles that were previously elusive. By leveraging the complementary strengths of molecular surface representations and advanced AI algorithms, scientists can now explore chemical space more efficiently, optimize molecular properties with greater precision, and drive transformative advancements in areas like drug development, materials engineering, and catalysis. In this review, we aim to provide an overview of recent advancements in the field of molecular surface analysis and its integration with AI techniques. These AI-driven approaches have led to significant advancements in various downstream tasks, including interface site prediction, protein-protein interaction prediction, surface-centric molecular generation and design.

Breast cancer (BC) remains one of the most common malignancies among women worldwide, with persistently poor prognosis despite advancements in diagnostics and therapies. Long non-coding RNAs (lncRNAs) and coagulation-related genes (CRGs) are increasingly recognized for their roles in prognosis and immune modulation. Using transcriptomic data from 1,045 BC patients in TCGA, we identified CRG-associated lncRNAs via coexpression analysis (Pearson |R|> 0.4, p < 0.001) and constructed a prognostic model through univariate Cox analysis, LASSO regression with tenfold cross-validation (λ = 0.05), and multivariate Cox analysis. The model stratified patients into high- and low-risk groups with distinct overall survival (HR = 3.21, p < 0.001) and demonstrated robust predictive accuracy (AUC = 0.795 at 1 year). Functional enrichment revealed immune-related pathways (e.g., cytokine signaling, PD-L1 regulation), and high-risk patients exhibited elevated tumor mutational burden (TMB) and PD-L1 expression, suggesting enhanced immunotherapy responsiveness. Drug sensitivity analysis identified 5 targeted agents (e.g., BIBW2992) with differential efficacy between risk groups. This CRG-lncRNA signature provides a novel tool for prognosis prediction and personalized immunotherapy in BC, illuminating crosstalk between coagulation and immune pathways.

Radiotherapy is an important management for non-small cell lung cancer (NSCLC). Although long non-coding RNAs (lncRNAs) have been reported to be involved in modulating radiosensitivity, the underlying mechanisms are still largely unclear. Here, we found that tumor suppressor WDR11-DT is a novel radiation-induced lncRNA, which is transcriptionally regulated by SPDEF, in NSCLC. In contrast to normal tissues, WDR11-DT is down-regulated in NSCLC specimens and its low expression was associated with poor prognosis of patient receiving radiotherapy. Importantly, WDR11-DT can markedly enhance NSCLC cells' radiosensitivity in vitro and in vivo. WDR11-DT functions through distinct mechanisms via binding different proteins. WDR11-DT facilitates interactions between PARP1 and its E3 ligase TRIP12, promotes PARP1 protein degradation and suppresses PARP1-controlled Single-strand breaks (SSBs) repair. Additionally, WDR11-DT binds RNA-bind protein HNRNPK, represses its functions in improving RNA stability of homologous recombination (HR) genes, decreases expression of BRCA1, ATM, BLM and RAD50, and suppresses radiotherapy-triggered HR repair. WDR11-DT-induced dual restraints of PARP1 and the HR pathway lead to the accumulation of double-strand breaks as well as synthetic lethal effects of malignant cells, which, thereby, enhances radiosensitivity and inhibits progression of lung cancer. These results extend our current knowledge of radio-biology and elucidate that WDR11-DT may be a new target for boosting cancer radiotherapy.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer mortality. Despite advancements in gene targeted therapies and immunotherapies, high heterogeneity contributes to limited efficacy and therapeutic resistance. Ubiquitination, a crucial post-translational modification that regulates protein stability and degradation, plays a significant role in cancer pathogenesis by influencing key oncogenic pathways and tumour progression. This review systematically explores the ubiquitin-proteasome system (UPS) and its potential as a therapeutic target for NSCLC. We highlight recent preclinical and clinical studies focusing on ubiquitination-related biomarkers, drug targets and emerging therapies like proteasome inhibitors and Proteolysis-targeting chimeras (PROTACs). By exploring the impact of the UPS on tumour biology, the progression of NSCLC and its response to therapy, we aim to underscore the potential of targeting the ubiquitination-deubiquitination system as a complementary or synergistic approach to existing therapeutic strategies in NSCLC, thereby enhancing patient outcomes and overcoming treatment resistance.

tRNA-derived small RNAs (tsRNAs) are non-coding small RNAs that are produced through the precise cleavage of tRNA molecules under specific conditions. tsRNA has multiple functions, including inhibiting translation, acting in association with classical small RNA effector mechanisms, or acting in conjunction with Argonaute proteins that affect cell proliferation, migration, cycle, and apoptosis. Recent studies have revealed the clinical potential of tsRNAs in numerous diseases. This article aims to provide a comprehensive and up-to-date review of the classification and biological function of tsRNAs in gastrointestinal diseases. Furthermore, this review explores the underlying mechanisms by which tsRNAs are believed to exert their effects in both tumor and non-tumor digestive tract diseases. Therefore, specific tsRNAs prove promising for disease diagnosis, prognosis prediction, and therapeutic interventions as novel biomarkers for digestive tract diseases.

Cancer constitutes a significant public health concern, and addressing the challenge of cancer holds paramount importance and requires immediate attention. Epigenetic alterations, encompassing DNA methylation, have emerged as pivotal contributors to the development of diverse cancer types. These modifications exert their influence by modulating chromatin structure, gene expression patterns and other nuclear processes, thereby influencing cancer pathogenesis. Over the last two decades, an increasing body of evidence has established the involvement of DNA methyltransferase 1 (DNMT1) in various aspects of cancer development, including tumorigenesis, aggressiveness and treatment response. Furthermore, non-coding RNAs (ncRNAs), such as microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), are increasingly recognised as significant modulators in diverse biological processes, encompassing metastasis, apoptosis, cell proliferation and differentiation. Several recent studies have elucidated the intricate relationship between epigenetic machinery, specifically DNMT1, and the expression of ncRNAs in the context of cancer. In this review, we provide a comprehensive overview of the interaction between DNMT1 and ncRNAs in cancer pathogenesis. Furthermore, we discuss the important role of the ncRNAs-DNMT1 axis in cancer stem cells and cancer therapy resistance as critical issues in cancer therapy. Finally, we demonstrate that herbal medicine and synthetic RNA molecules regulate DNMT1 activity and hold great promise in cancer treatment.

The study of cancer, its initiation, and its mechanisms of progression has been a focal point in science for more than a century. Despite controversies among scientists, there is a growing consensus to determine the moment when a cell gains the capacity to be transformed and whether this mechanism is to be attributed to germinal or somatic events, or possibly both. The case of the Xavante Indians is a beacon for this journey, pointing toward the importance of genetic diversity in shaping our approach to cancer research and treatment. As we incorporated these lessons into clinical practice, we embarked on a new era of personalized preventative healthcare strategies against cancer. Based on recent data, we comment on the low germinal mutational load and low cancer incidence. Statistical analyses reveal a significantly lower mutation burden in Xavante women compared to global populations (p < 0.0001), including rare deleterious variants in cancer-associated genes. Additionally, polygenic risk scores (PRS) for breast cancer are markedly lower in Xavante (mean PRS ∼35) compared to TCGA cohorts (∼80-90) (p < 0.0001). The absence of breast cancer cases in Xavante is statistically significant when compared to expected rates (p < 0.001), reinforcing the hypothesis of a protective genetic landscape.

5-Methylcytosine (m5C) modification is an important type of RNA methylation. Diverse noncoding RNAs can undergo m5C modification and play important roles in tumour development, but circRNA m5C modifications have not been fully revealed in tumours. Here, circFAM190B, which was significantly overexpressed in lung cancer cells and tissues, was identified by constructing a differential expression profile of m5C-modified circRNAs. circFAM190B was found to be associated with lung cancer stage and prognosis. Moreover, we proposed the novel hypothesis that NSUN2 can mediate circFAM190B m5C modification and enhance circFAM190B stability in an m5C-dependent manner. We also clarified the biological function of circFAM190B in significantly promoting the development of lung cancer. Mechanistically, circFAM190B targets SFN and regulates its ubiquitination, thereby inhibiting cellular autophagy through the SFN/mTOR/ULK1 pathway and ultimately promoting lung cancer development. This study reveals the existence of m5C modification of circRNAs, and circRNAs modified by m5C can play important roles in the development of lung cancer, which provides a new theoretical basis for elucidating the molecular mechanism of lung cancer development.

Long non-coding RNAs (lncRNAs) have been shown to be integral in a variety of biological processes and significantly influence the progression of several human diseases. Their involvement in disease mechanisms makes them crucial targets for research in disease biomarker identification. Understanding the intricate relationships between lncRNAs and diseases can offer valuable insights for advancing diagnostic, prognostic and therapeutic strategies. In light of this, we propose a recommendation-system-based model utilizing matrix factorization with disease neighborhood regularization to effectively infer disease-related lncRNAs (NRMFLDA). This approach leverages the power of matrix factorization techniques while incorporating disease neighborhood regularization to enhance the accuracy and reliability of lncRNA-disease association predictions. Consequently, NRMFLDA exhibits outstanding performance, achieving AUC scores of 0.9143 and 0.8993 in both leave-one-out and five-fold cross-validation, surpassing the performance of four previous models. This demonstrates its effectiveness and robustness in accurately predicting disease-related lncRNAs. We believe that NRMFLDA will not only provide innovative approaches for uncovering lncRNA-disease associations but also contribute significantly to the identification of novel biomarkers for various diseases, thereby advancing diagnostic and therapeutic strategies.

RNA methylation is a vital epigenetic modification that regulates gene expression by influencing RNA processes such as transcription, degradation, translation, and transport. Aberrant methylation, including modifications like m6A, m5C, m1A, m7G, and m3C, is closely linked to tumorigenesis and progression. Liquid biopsy, a non-invasive technique analyzing tumor markers in body fluids, offers significant potential for early diagnosis and dynamic monitoring. In this context, RNA methylation, due to its tumor-specific properties, is emerging as a valuable marker. However, significant challenges remain in its clinical application. This review explores the roles of RNA methylation in cancer, recent advances in detection technologies, and its potential as a liquid biopsy marker in tumor management. It highlights its promising applications in cancer diagnosis, prognosis, and personalized treatment in the era of precision oncology.

Human papillomavirus (HPV), a DNA virus, is a well-documented causative agent of several cancers, including cervical, vulvar, vaginal, penile, anal, and head & neck cancers. Major factors contributing to HPV-related cancers include persistent infection and the oncogenic potential of particular HPV genotypes. High-risk HPV strains, particularly HPV-16 and HPV-18, are responsible for over 70% of cervical cancer cases worldwide, as well as a significant proportion of other genital and head and neck cancers. At the molecular level, the oncogenic activity of these viruses is driven by the overexpression of E6 and E7 oncoproteins. These oncoproteins dysregulate the cell cycle, inhibit apoptosis, and promote the accumulation of DNA damage, ultimately transforming normal cells into cancerous ones. This review aims to provide a comprehensive overview of the recent advances in HPV-related cancer biology and epidemiology. The review highlights the molecular pathways of HPV-driven carcinogenesis, focusing on the role of viral oncoproteins in altering host cell targets and disrupting cellular signalling pathways. The review explores the therapeutic potential of these viral proteins, and discusses current diagnostic and treatment strategies for HPV-associated cancers. Furthermore, the review highlights the critical role of HPV in the development of various malignancies, emphasizing the persistent challenges in combating these cancers despite advancements in vaccination and therapeutic strategies. We also emphasize recent breakthroughs in utilizing biomarkers to monitor cancer therapy responses, such as mRNAs, miRNAs, lncRNAs, proteins, and genetic markers. We hope this review will serve as a valuable resource for researchers working on HPV, providing insights that can guide future investigations into this complex virus, which continues to be a major contributor to global morbidity and mortality.

Papillary renal cell carcinoma (pRCC), particularly type 2, is associated with a poor prognosis. This study aimed to identify molecular mechanisms underlying pRCC progression and explore potential therapeutic targets to improve patient outcomes.

TPX2 expression was analyzed in tumor samples from patients with type 2 pRCC. In vitro experiments were conducted to assess the effects of TPX2 and LINC00894 knockdown and overexpression on the proliferation and migration of Caki-2 and ACHN cells. Immunohistochemical analysis of tissue microarrays was performed to evaluate the associations between TPX2 expression and clinicopathological characteristics in type 2 pRCC patients.

Elevated TPX2 expression was significantly associated with a worse prognosis in type 2 pRCC patients and served as an independent risk factor for overall survival. Knockdown of TPX2 in Caki-2 and ACHN cells significantly reduced cell proliferation and migration. Additionally, LINC00894 was highly expressed in type 2 pRCC and correlated with poor prognosis. Mechanistically, miR-660-5p targeted the TPX2 3' UTR, promoting TPX2 degradation, while LINC00894 competitively bound to miR-660-5p, protecting TPX2 from miRNA-mediated degradation and exerting a pro-oncogenic effect. Immunohistochemical analysis revealed significant correlations between TPX2 expression and clinicopathological features, including tumor thrombus volume, tumor diameter, pathological TNM stage, and Fuhrman grade.

This study underscores the critical role of TPX2 in type 2 pRCC progression and highlights its potential as a prognostic biomarker and therapeutic target. The TPX2/LINC00894/miR-660-5p regulatory axis provides novel insights into the molecular mechanisms driving pRCC and offers a promising avenue for improving patient prognosis.

Circular RNAs (circRNAs) exhibit dysregulation in non-small cell lung cancer (NSCLC) and regulate the malignant biological behavior of NSCLC. The N6-methyladenosine (m6A) modification of circRNAs plays a critical role in multiple malignant tumors, and their biological relevance in NSCLC is unclear. Herein, this study was conducted to investigate the novel functional mechanism of highly expressed circ_0000517 in NSCLC by developing in vitro experiments. We found that circ_0000517 was upregulated in NSCLC tissues and cells, and that increased circ_0000517 expression was associated with m6A modification. Biologically, silenced circ_0000517 hindered the proliferation, colony formation, migration and invasion of NSCLC cells in vitro, and also suppressed the EMT-related process. Mechanistically, highly expressed circ_0000517 activated CDH6 expression and EMT evolution through sponging miR-1233-3p. Notably, miR-1233-3p had the opposite effect and reversed the promotion effect of circ_0000517 on the malignant biological behavior of NSCLC cells. Our study revealed a promising novel endogenous regulatory network that m6A-modified circ_0000517 accelerated malignant evolution of NSCLC by targeting the miR-1233-3p/CDH6 axis.

Non-coding RNAs (ncRNAs), as critical regulators of gene expression, play a pivotal role in the modulation of pyroptosis and exhibit a close association with a wide range of diseases. Pyroptosis is a form of programmed cell death mediated by inflammasomes, characterized by cell membrane perforation, release of inflammatory cytokines, and a robust immune response. Recent studies have revealed that ncRNAs influence the initiation and execution of pyroptosis by regulating the expression of pyroptosis-related genes or modulating associated signaling pathways. This review systematically summarizes the molecular mechanisms and applications of ncRNAs in diseases such as cancer, infectious diseases, neurological disorders, cardiovascular diseases, and metabolic disorders. It further explores the potential of ncRNAs as diagnostic biomarkers and therapeutic targets, elucidates the intricate interactions among ncRNAs, pyroptosis, and diseases, and provides novel strategies and directions for the precision treatment of related diseases.

Circular RNAs (circRNAs) are a type of non coding RNA that possess unique single stranded circular structures formed through reverse splicing mechanisms. Due to the lack of a free end that is typically susceptible to degradation by nucleases, circular RNAs exhibit resistance to ribonuclease R, making them highly stable in eukaryotic cells. The complex relationship between circRNA dysregulation and various pathophysiological conditions, especially cancer. Tumor microenvironment (TME) is a collective term for various components surrounding tumors and is an important factor affecting tumor development. Simultaneous infiltration of TME by different types of immune cells; These immune cells interact with the TME, collectively forming the so-called "tumor immune microenvironment". The complex interactions between tumor cells and TME profoundly affect the behavior of malignant tumors, and circRNAs derived from tumor cells and TME cell components have become important mediators of immune response and evasion within the TME. CircRNAs can directly or indirectly regulate immune cells, thereby modulating anti-tumor immunity. This review highlights how circRNAs, especially those encapsulated in extracellular vesicles like exosomes, influence the differentiation, chemotaxis, and anti-tumor immune functions of immune cells within the TME. Metabolic reprogramming plays an important role in this process. The process of circRNAs regulating tumor immunity is affected by multiple factors, such as hypoxia and viral infection. This review emphasizes the roles of the interaction between circRNAs and the TME in tumor immune regulation and prospects the guiding significance of circRNAs in tumor immune checkpoint therapy.

Breast cancer, a highly prevalent form of cancer worldwide, has observed a steady increase in its prevalence over the past few decades. This rise can be attributed to the complex nature of the disease, characterized by its heterogeneity, ability to metastasize, and resistance to various treatment. In the field of cancer research, long non-coding RNAs (lncRNAs) are of special interest, which play an important role in the development and progression of various tumors, including breast cancer. LncRNAs affect the tumor microenvironment by attracting diverse immunosuppressive factors and controlling the differentiation of immune cells, often referred to as myeloid and lymphoid cells, which contributes to immune escape of tumor cells. Among the lncRNA families, the small nucleolar RNA host gene (SNHG) family has been found to be dysregulated in breast cancer. These SNHGs have been implicated in crucial cellular processes such as cell proliferation, invasion, migration, resistance to therapies, apoptosis, as well as immune cell regulation and differentiation. Consequently, they have great potential as diagnostic and prognostic biomarkers as well as potential therapeutic targets for breast cancer. In this comprehensive review, we aim to summarize the recent advances in the study of SNHGs in breast cancer pathogenesis and their role in regulating the activity of immune cells in the tumor microenvironment through affecting SNHGs/miRNA/mRNA pathways, with the aim of providing new insights into the treatment of breast cancer.

Pregnancy-related medical complications such as gestational diabetes mellitus (GDM) are common and associated with several obstetric and neonatal problems. There is growing evidence that microRNAs (miRNAs) are essential players in the pathophysiology of GDM. This study aimed to assess how particular miRNAs and the genes they target are expressed in GDM.

A GDM cell model was created using BeWo cells cultured in hyperglycemic (HG) conditions (25 mM glucose). Low-glucose (LG) conditions (5.5 mM glucose) were used for the BeWo cells in the control group. Differentially expressed genes (DEGs) in BeWo cells were identified by high-throughput sequencing and their levels verified in placental samples from GDM patients and controls using RT-PCR. Furthermore, the target genes of the DEGs were verified using dual-luciferase reporter assays.

High-throughput sequencing revealed 220 DEGs in BeWo cells. Among these, miR-3687 was significantly upregulated, while Follistatin-like 3 (FSTL3) was downregulated in BeWo cells under HG conditions. The high-throughput sequencing results were corroborated by RT-PCR, which showed that placental samples from GDM patients had significantly lower levels of FSTL3 expression and substantially higher amounts of miR-3687 expression compared to control samples. FSTL3 was established as a direct target of miR-3687 as shown by dual-luciferase reporter assays.

The increase of miR-3687 might facilitate the onset and advancement of GDM by suppressing FSTL3. This discovery offered a new perspective on the molecular underpinnings of GDM and indicated possible targets for therapeutic intervention.

Ovarian dysfunctions, encompassing conditions such as polycystic ovary syndrome (PCOS), premature ovarian failure (POF), premature ovarian insufficiency (POI), and diminished ovarian reserve (DOR), are closely linked to disruptions in follicular development, often tied to granulosa cell (GC) abnormalities. Despite ongoing research, the precise mechanisms underlying these dysfunctions remain elusive. Increasing evidence highlights the pivotal role of non-coding RNAs (ncRNAs) in the pathogenesis of ovarian dysfunctions. As transcripts that do not encode proteins, ncRNAs are capable of regulating gene expression at various levels. They influence GCs by modulating key biological processes including proliferation, apoptosis, autophagy, cell cycle progression, steroidogenesis, mitochondrial function, inflammatory responses, and aging. Disruptions in GC development and function can lead to impaired follicular development, consequently contributing to ovarian dysfunctions. Thus, ncRNAs are likely integral to the regulatory mechanisms underlying these pathologies, exhibiting distinct expression patterns in affected individuals. This review delves into the regulatory roles of ncRNAs in GCs and their implications for ovarian dysfunctions (PCOS, POF, POI, DOR), offering insights into potential biomarkers for ovarian function assessment and novel therapeutic approaches for treating these conditions.

MiRNA expression profiles may serve as valuable biomarkers for early cancer diagnosis. However, the detection of miRNA remains greatly challenging due to its shorter length and lower abundance in cells. Electrochemical biosensors based on DNA nanostructures have attracted significant attention due to their improved capture efficiency, high sensitivity, and ease of miniaturization, but the complex construction process, non-specific interactions among DNA probes, and their low stability continue to severely restrict their widespread application in clinical diagnostics. Therefore, developing robust and sensitive methods for miRNA analysis is still of great value.

We describe an ultra-sensitive electrochemical biosensor for miRNA by integrating the PNA-DNA2 three-way junction (3WJ) nanostructure with target-recycling catalytic hairpin assembly (CHA) and hybridization chain reaction (HCR) dual cascade isothermal amplification. The target miRNA triggers CHA amplification, resulting in the generation of substantial quantities of double-stranded DNA (dsDNA) products. These dsDNA are subsequently captured by PNA probes immobilized on the electrode surface, leading to the formation of a densely packed layer of PNA-DNA2 3WJ nanostructure. Subsequently, the single-stranded termini of the two branches extending from 3WJ function as promoters to initiate the HCR, resulting in the formation of a layer of intricately intertwined branched long dsDNA molecules, which could adsorb substantial quantities of [Ru(NH3)6]3+, thereby significantly amplifying the electrochemical signal. This electrochemical biosensor exhibits exceptional sensitivity towards miRNA-21, achieving a detection limit as low as 2.9 aM while effectively discriminating single base mutations.

This represents the first electrochemical system for miRNA detection by integrating the PNA-DNA2 3WJ with CHA-HCR dual cascade isothermal amplification. The robust, specific and ultrasensitive feature makes cancer cell miRNA monitoring possible, suggesting its great application prospect as a promising sensing platform for monitoring various miRNA biomarkers in cancer diagnostics.

In the realms of bioengineering and biopharmaceuticals, there exists a critical demand for advanced genetic tools that can interact with specific cell signaling pathways to accurately identify and target various cell types. This research introduces the innovative CRISPR-ADAReader system, which enables precise manipulation of cell activity through sensing target RNA. Featuring both positive and negative feedback loops, the system allows for tailored regulation across different cell types in response to various internal signals, showcasing exceptional programmability, specificity, and sensitivity. By choosing distinct RNAs as activation signals, the CRISPR-ADAReader efficiently monitors and alters targeted cell behaviors. In a case study focusing on retinoblastoma treatment, the system distinctively initiates positive feedback and self-silencing actions by detecting MCYN and Rb transcripts, thus safeguarding normal retinal pigment epithelial cells while promoting apoptosis in cancer cells. Moreover, the CRISPR-ADAReader demonstrates significant anti-tumor effectiveness in live models, markedly reducing retinoblastoma cell proliferation through the activation of several cancer-suppression pathways, outperforming the capabilities of the ADAR-sensor. Notably, the system also shows an excellent in vivo safety profile. In conclusion, the CRISPR-ADAReader system represents a groundbreaking method for the detection and editing of RNA, offering a potent instrument for the customized and precise governance of cell behavior.

Long non‑coding RNAs (lncRNAs) are key players in the regulation of gene expression by mediating epigenetic and epitranscriptomic modification. Dysregulation of lncRNAs is implicated in tumor initiation, progression and metastasis. lncRNAs modulate chromatin structure and gene transcription by recruiting epigenetic regulators, including DNA‑ or histone‑modifying enzymes. Additionally, lncRNAs mediate chromatin remodeling and enhancer‑promoter long‑range chromatin interactions to control oncogene expression by recruiting chromatin organization‑associated proteins, thereby promoting carcinogenesis. Furthermore, lncRNAs aberrantly induce oncogene expression by mediating epitranscriptomic modifications, including RNA methylation and RNA editing. The present study aimed to summarize the regulatory mechanisms of lncRNAs in cancer to unravel the complex interplay between lncRNAs and epigenetic/epitranscriptomic regulators in carcinogenesis. The present review aimed to provide a novel perspective on the epigenetic and epitranscriptomic roles of lncRNAs in carcinogenesis to facilitate identification of potential biomarkers and therapeutic targets for cancer diagnosis and treatment.

The occurrence of diabetic cardiomyopathy (DCM) can be independent of several risk factors such as hypertension and myocardial ischemia, which can lead to heart failure, thus seriously threatening human health and life. Sustained hyperglycemic stimulation can induce cardiomyocyte apoptosis, which is recognized as the pathological basis of DCM. It has been demonstrated that dysregulation induced by apoptosis is closely associated to progression of DCM, but mechanisms behind it requires further clarification. Currently, increasing evidence has shown that non-coding RNA (ncRNA), especially microRNA, long-chain non-coding RNA (lncRNA), and circular RNA (circRNA), play a regulative role in apoptosis, thus affecting the progression of DCM. Notably, some ncRNAs have also exhibit potential significance as biomarkers and/or therapeutic targets for patients with DCM. In this review, recent findings regarding the potential mechanisms of ncRNA in regulating apoptosis and their role in the progression of DCM were systematically summarized in this research. The conclusion reveals that ncRNA abnormalities exert a crucial role in pathological changes of DCM, which offers potential therapeutic targets for the prevention of DCM.

Toll-like receptors (TLRs) are central components of the innate immune system as they recognize molecular patterns associated with pathogens and cellular damage and initiate immune responses using MyD88- and TRIF-dependent pathways. In contrast to being very useful for immune defense, dysregulated TLR signaling may be involved in diseases, such as cancer and autoimmune conditions. In cancer, TLRs create an environment that supports tumorigenesis and growth. In addition to this, a class of multifunctional noncoding RNAs (ncRNAs), including miRNAs, lncRNAs, and circRNAs, regulate gene expression without encoding proteins. MiRNAs regulate gene expression in a fine-tuned manner, while lncRNAs and circRNAs do so via diverse mechanisms. Notably, these ncRNAs interact, where lncRNAs and circRNAs function as competing endogenous RNAs and ceRNA, affecting miRNA activity. This interaction has a vital role in cancer pathology, in influencing that of various oncogenes and tumor suppressors in the tumor microenvironment; hence, modulation of ncRNAs could also be a great promising therapeutic approach. In this context, interplay between TLRs and ncRNAs is of paramount importance as they influence various parameters of the tumor microenvironment. TLR signaling works upon the expression of ncRNAs, while ncRNAs work back to regulate TLR signaling in return. An example of this includes miRNA targeting of components of the TLR; lncRNAs induced by TLR signaling possibly would favor tumor progression. Pharmacological interventions directed toward inhibiting these TLR pathways could be the model to halt malignancy by hampering pro-tumor inflammation and boosting immune responses against neoplasms. Hence, the review will highlight the complicated contrast of ncRNAs and TLRs within human cancer. By connecting the mechanisms, the researchers may study more about tumorigenesis and gather up new, innovative notions regarding therapeutic targeting.

Pancreatic cancer is an aggressive tumor with high metastatic potential which leads to decreased survival rate and resistance to chemotherapy and immunotherapy. Nearly 90% of pancreatic cancer comprises pancreatic ductal adenocarcinoma (PDAC). About 80% of diagnoses takes place at the advanced metastatic stage when it is unresectable, which renders chemotherapy regimens ineffective. There is also a dearth of specific biomarkers for early-stage detection. Advances in next generation sequencing and single cell profiling have identified molecular alterations and signatures that play a role in PDAC progression and subtype plasticity. Most chemotherapy regimens have shown only modest survival benefits, and therefore, translational approaches for immunotherapies and combination therapies are urgently required. In this review, we have examined the immunosuppressive and dense stromal network of tumor immune microenvironment with various metabolic and transcriptional changes that underlie the pro-tumorigenic properties in PDAC in terms of phenotypic heterogeneity, plasticity and subtype co-existence. Moreover, the stromal heterogeneity as well as genetic and epigenetic changes that impact PDAC development is discussed. We also review the PDAC interaction with sequestered cellular and humoral components present in the tumor immune microenvironment that modify the outcome of chemotherapy and radiation therapy. Finally, we discuss different therapeutic interventions targeting the tumor immune microenvironment aimed at better prognosis and improved survival in PDAC.

In recent years, research on the relationship between papillary thyroid carcinoma (PTC) and long non-coding RNAs (lncRNAs) has been burgeoning. However, there has not been an analysis of the regulatory mechanisms of these lncRNAs in all tumors, nor a comprehensive categorization and comparison of these mechanisms. This review aims to uncover whether PTC-related lncRNAs also play an important role in other tumors and to identify a common pattern of action.

We conducted a statistical analysis of lncRNAs related to PTC that have been reported during the period from Jan 2022 to May 2024 through searching in the Embase, Web of Science, and PubMed databases, focusing on those with greater research value. Using them as the focal points of our study, we compiled data on their different regulatory mechanisms across various malignant tumors, emphasizing key findings.

This comprehensive analysis not only provides valuable insights into potential regulatory mechanisms of these lncRNAs in PTC but also serves as a reference for exploring their broader regulatory networks within cancer. The principal discovery is that lncRNAs associated with PTC can competitively interact with microRNAs (miRNAs). This interaction influences miRNA-targeted messenger RNA (mRNA) and the expression of cancer-related proteins, ultimately facilitating the progression of PTC as well as other malignant tumors.

The lncRNAs associated with PTC exert regulatory functions in other malignancies as well and possess similar regulatory mechanisms. This provides a molecular basis for the future development of relevant targeted therapies.

Liver cancer, characterized by its insidious nature, aggressive invasiveness, and propensity for metastasis, has witnessed a sustained increase in both incidence and mortality rates in recent years, underscoring the urgent need for innovative diagnostic and therapeutic approaches. Emerging research indicates that CircRNAs (circular RNAs) are abundantly and stably present within cells, with their expression levels closely associated with the progression of various malignancies, including hepatocellular carcinoma. In the context of liver cancer progression, circRNAs exhibit promising potential as highly sensitive diagnostic biomarkers, offering novel avenues for early detection, and also function as pivotal regulatory factors within the carcinogenic process. This study endeavors to elucidate the biogenesis, functional roles, and underlying mechanisms of circRNAs in hepatocellular carcinoma, thereby providing a fresh perspective on the pathogenesis of liver cancer and laying a robust foundation for the development of more precise and effective early diagnostic tools and therapeutic strategies.

The apelinergic system exerts multiple biological activities in human pathologies, including cancer. Overactivation of apelin/APJ, which has been detected in many malignant tumors, and the strong correlation with progression-free and overall survival, suggested the role of an oncogene for the apelin gene. Emerging evidence sheds new light on the effects of apelin on cellular functions and homeostasis in cancer cells and supports a direct role for this pathway on different hallmarks of cancer: "sustaining proliferative signaling", "resisting cell death", "activating invasion and metastasis", "inducing/accessing vasculature", "reprogramming cellular metabolism", "avoiding immune destruction" and "tumor-promoting inflammation", and "enabling replicative immortality". This article reviews the currently available literature on the intracellular processes regulated by apelin/APJ, focusing on those pathways correlated with tumor development and progression. Furthermore, the association between the activity of the apelinergic axis and the resistance of cancer cells to oncologic treatments (chemotherapy, immunotherapy, radiation) suggests apelin/APJ as a possible target to potentiate traditional therapies, as well as to develop diagnostic and prognostic applications. This issue will be also covered in the review.

The ZBTB (zinc finger and BTB domain-containing) protein family comprises a significant class of transcription factors that interact with various corepressors and histone/protein-modifying enzymes. This interaction facilitates chromatin remodeling and the regulation of gene silencing or activation, thereby playing a crucial role in cancer progression. However, the biological effects and molecular mechanisms of ZBTB6, a member of the ZBTB family, in cancer remain unclear.

The expression levels of ZBTB6 in breast cancer (BC) were investigated through public database queries, real-time quantitative PCR (qRT‒PCR), and Western blot analysis. The effects of ZBTB6 on BC cell viability were assessed via MTT assays. Flow cytometry was utilized to analyze the cell cycle distribution and apoptosis. Additionally, cell-derived xenograft experiments were conducted to study the impact of ZBTB6 on BC growth in vivo. The relationship between ZBTB6 and the ARHGAP6 promoter was evaluated via bioinformatics predictions, chromatin immunoprecipitation (ChIP) coupled with qRT‒PCR, and luciferase reporter assays.

Our study demonstrated that ZBTB6 is highly expressed in primary BC specimens and cell lines and strongly correlated with tumor grade and poor prognosis. In vitro, ZBTB6 knockdown inhibited cell viability and cell cycle progression while promoting apoptosis; conversely, ZBTB6 overexpression elicited the opposite effects. In vivo, the inhibition of ZBTB6 expression in BC cells significantly suppressed tumor growth. Furthermore, we identified ARHGAP6 as a transcriptional target downstream of ZBTB6, with ZBTB6 binding to the promoter region of ARHGAP6 to repress its transcription. Notably, ARHGAP6 can exert an inhibitory effect on tumors by attenuating STAT3 activity. Our results indicate that ZBTB6 overexpression enhances the STAT3 signaling pathway, whereas ARHGAP6 overexpression counteracts the effects of ZBTB6 overexpression in BC cells.

These findings suggest that ZBTB6 promotes breast cancer progression by repressing the transcription of ARHGAP6 and activating the STAT3 signaling pathway. Consequently, ZBTB6 may serve as a potential prognostic biomarker or therapeutic target for breast cancer patients.

Long noncoding RNAs (lncRNAs) cover a large class of transcribed RNA molecules that are more than 200 nucleotides in length. An increasing number of studies have shown that lncRNAs control gene expression through different mechanisms and play important roles in a range of biological processes including growth, cell differentiation, proliferation, apoptosis, and invasion. TUG1 was originally discovered in a genomic screen of taurine-treated mouse retinal cells. Previous evidences pointed out that lncRNA TUG1 could inhibit apoptosis and the release of inflammatory factors, improve mitochondrial function, thereby protecting cells from damage, and showing a protective role of TUG1 in diseases. Given that TUG1 has multiple targets and can interfere with multiple steps in the oncogenic process, it has been proposed as a therapeutic target. In this review, we summarize the research progress of lncRNA TUG1 in kidney diseases in the past 8 years, and discuss its related molecular mechanisms.

Aptamers bind to their targets with exceptional affinity and specificity. However, their intracellular application is hampered by the lack of knowledge about the effect of the cellular milieu on the RNA structure/stability. In this study, cellular crowding was mimicked using polyethylene glycol (PEG), and the crucial role of Mg2+ ions in stabilizing the structure of an RNA aptamer was investigated. Increasing the concentration of Mg2+ or PEG increased the thermal stability of the aptamer. The crowding effect lowered the requirement of the Mg2+ ion to form the binding-competent conformer of the aptamer. This suggests that crowding and other factors may compensate for a lower concentration of Mg2+ for proper folding of aptamers inside cells. Selective 2'-hydroxyl acylation and primer extension (SHAPE) probing permitted residue-level analysis of the aptamer. Mg2+ and/or PEG were shown to be involved in increasing the rigidity or flexibility of different regions of the aptamer. Fluorescence correlation spectroscopy showed a significantly low hydrodynamic radius (RH) in the presence of molecular crowders and Mg2+ ions. We believe that the decreased water activity due to crowding may be responsible for reduced RH. Our results show that in a crowded environment, the RNA aptamer was exposed to conformers that were not available to it in simple buffer solutions or solely in the presence of lower concentrations of Mg2+.

Metabolic reprogramming is a hallmark of cancer, crucial for supporting the rapid energy demands of tumor cells. MYC, often deregulated and overexpressed, is a key driver of this shift, promoting the Warburg effect by enhancing glycolysis. However, there remains a gap in understanding the mechanisms and factors influencing MYC's metabolic roles. Recently, non-coding RNAs (ncRNAs) have emerged as important modulators of MYC functions. This review focuses on ncRNAs that regulate MYC-driven metabolism, particularly the Warburg effect. The review categorizes these ncRNAs into three main groups based on their interaction with MYC and examines the mechanisms behind these interactions. Additionally, we explore how different types of ncRNAs may collaborate or influence each other's roles in MYC regulation and metabolic function, aiming to identify biomarkers and synthetic lethality targets to disrupt MYC-driven metabolic reprogramming in cancer. Finaly, the review highlights the clinical implications of these ncRNAs, providing an up-to-date summary of their potential roles in cancer prognosis and therapy. With the recent advances in MYC-targeted therapy reaching clinical trials, the exciting potential of combining these therapies with ncRNA-based strategies holds great promise for enhancing treatment efficacy.

Lung cancer poses a serious threat to human health, but its molecular mechanisms remain unclear. Circular RNAs (circRNAs) are closely associated with tumour progression, and the important role of 8-oxoguanine (o8G) modification in regulating the fate of RNA has been gradually revealed. However, o8G modification of circRNAs has not been reported. We identified circPLCE1, which is significantly downregulated in lung cancer, and further investigated the o8G modification of circPLCE1 and the related mechanism in lung cancer progression.

We identified differentially expressed circRNAs by RNA high-throughput sequencing and then conducted methylated RNA immunoprecipitation (MeRIP), immunofluorescence (IF) analysis, crosslinking immunoprecipitation (CLIP) and actinomycin D (ActD) assays to explore circPLCE1 o8G modification. The biological functions of circPLCE1 in vivo and in vitro were clarified via establishing a circPLCE1 silencing/overexpression system. Tagged RNA affinity purification (TRAP), RNA Immunoprecipitation (RIP) and coimmunoprecipitation (Co-IP) assays, and pSIN-PAmCherry-KFERQ-NE reporter gene were used to elucidate the molecular mechanism by which circPLCE1 inhibits lung cancer progression.

This study revealed that reactive oxygen species (ROS) can induce circPLCE1 o8G modification and that AUF1 can mediate a decrease in circPLCE1 stability. We found that circPLCE1 significantly inhibited lung cancer progression in vitro and in vivo and that its expression was associated with tumour stage and prognosis. The molecular mechanism was elucidated: circPLCE1 targets the HSC70 protein, increases its ubiquitination level, regulates ATG5-dependent macroautophagy via the chaperone-mediated autophagy (CMA) pathway, and ultimately inhibits lung cancer progression.

o8G-modified circPLCE1 inhibits lung cancer progression through CMA to inhibit macroautophagy and alter cell fate. This study provides not only a new theoretical basis for elucidating the molecular mechanism of lung cancer progression but also potential targets for lung cancer treatment.

Recent progress in noncoding RNA research has highlighted transfer RNA-derived small RNAs (tsRNAs) as key regulators of gene expression, linking them to numerous cellular functions. tsRNAs, which are produced by ribonucleases such as angiogenin and Dicer, are classified based on their size and cleavage positions. They play diverse regulatory roles at the transcriptional, post-transcriptional, and translational levels. Furthermore, tRNAs undergo various modifications that influence their biogenesis, stability, functionality, biochemical characteristics, and protein-binding affinity. tsRNAs, with their aberrant expression patterns and modifications, act as both oncogenes and tumor suppressors. This review explores the biogenetic pathways of tsRNAs and their complex roles in gene regulation. We then focus on the importance of RNA modifications in tsRNAs, evaluating their impact on the biogenesis and biological functions on tsRNAs. Furthermore, we summarize recent data indicating that tsRNAs exhibit varied expression profiles across different cancer types, highlighting their potential as innovative biomarkers and therapeutic targets. This discussion integrates both existing and new knowledge about tsRNAs, emphasizing their importance in cancer biology and clinical advancement.

Long noncoding RNAs (lncRNAs) play numerous roles in cellular biology and alterations in lncRNA expression profiles have been implicated in a variety of cancers. Here, we identify and characterize a lncRNA, TRIM28 Interacting DNA damage repair Enhancing Noncoding Transcript (TRIDENT), whose expression is induced upon epithelial growth factor receptor (EGFR) activation, and which exerts pro-oncogenic functions in EGFR-driven non-small cell lung cancer. Knocking down TRIDENT leads to decreased tumor-cell proliferation in both in vitro and in vivo model systems and induces sensitization to chemotherapeutic drugs. Using ChIRP-MS analysis we identified TRIM28 as a protein interactor of TRIDENT. TRIDENT promotes phosphorylation of TRIM28 and knocking down TRIDENT leads to accumulation of DNA damage in cancer cells via decreased TRIM28 phosphorylation. Altogether, our results reveal a molecular pathway in which TRIDENT regulates TRIM28 phosphorylation to promote tumor cell growth and drug resistance. Our findings suggest that TRIDENT can be developed as a biomarker or therapeutic target for EGFR mutant non-small cell lung cancer.

Many biomolecules and signaling pathways are involved in the development of alcoholic liver disease (ALD). The molecular mechanisms of ALD are not fully understood and there is no effective treatment. Numerous studies have demonstrated the critical role of non-coding RNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), in ALD. miRNAs play an important regulatory role in the pathogenesis of ALD by controlling critical biological processes such as inflammation, oxidative stress, lipid metabolism, apoptosis and fibrosis. Among them, miR-155, miR-223 and miR-34a play a central role in these processes and influence the pathological process of ALD. In addition, lncRNAs are involved in regulating liver injury and repair by interacting with miRNAs to form a complex regulatory network. These findings help to elucidate the molecular mechanisms of ALD and provide a scientific basis for the development of new diagnostic markers and therapeutic targets. In this article, we review the roles and mechanisms of LncRNAs and miRNAs in ALD and their potential use as diagnostic markers and therapeutic targets.

Circular RNAs (circRNAs) have emerged as critical regulators in cancer biology, contributing to various cancer hallmarks, including cell proliferation, apoptosis, metastasis, and drug resistance. Defined by their covalently closed loop structure, circRNAs possess unique characteristics like high stability, abundance, and tissue-specific expression. These non-coding RNAs function through mechanisms such as miRNA sponging, interactions with RNA-binding proteins (RBPs), and modulating transcription and splicing. Advances in RNA sequencing and bioinformatics tools have enabled the identification and functional annotation of circRNAs across different cancer types. Clinically, circRNAs demonstrate high specificity and sensitivity in samples, offering potential as diagnostic and prognostic biomarkers. Additionally, therapeutic strategies involving circRNA mimics, inhibitors, and delivery systems are under investigation. However, their precise mechanisms remain unclear, and more clinical evidence is needed regarding their roles in cancer hallmarks. Understanding circRNAs will pave the way for novel diagnostic and therapeutic approaches, potentially improving patient outcomes.

In hepatocellular carcinoma (HCC), successful translation of experimental targets identified in mouse models to human patients has proven challenging. In this study, we used a comprehensive transcriptomic approach in mice to identify novel potential targets for therapeutic intervention in humans.

We analyzed combined genome-wide miRNA and mRNA expression data in three pathogenically distinct mouse models of liver cancer. Effects of target genes on hepatoma cell fitness were evaluated by proliferation, survival and motility assays. TCGA and GEO databases, in combination with tissue microarrays, were used to validate the mouse targets and their impact on human HCC prognosis. Finally, the functional effects of the identified targets on tumorigenesis and tumor therapy were tested in hydrodynamic tail vein injection-based preclinical HCC models in vivo.

The expression of miR-107 was found to be significantly reduced in mouse models of liver tumors of various etiologies and in cohorts of humans with HCC. Overexpression of miR-107 or inhibition of its novel target kinesin family member 23 (Kif23) significantly reduced proliferation by interfering with cytokinesis, thereby controlling survival and motility of mouse and human hepatoma cells. In humans, KIF23 expression was found to be a prognostic marker in liver cancer, with high expression associated with poor prognosis. Hydrodynamic tail vein injection of vectors carrying either pre-miR-107 or anti-Kif23 shRNA inhibited the development of highly aggressive c-Myc-NRAS-induced liver cancers in mice.

Disruption of the miR-107/Kif23 axis inhibited hepatoma cell proliferation in vitro and prevented oncogene-induced liver cancer development in vivo, offering a novel potential avenue for the treatment of HCC in humans.

Our study revealed the central role of the miR-107/KIF23 axis in controlling tumor cell fitness and hepatocellular carcinoma progression. The results demonstrate that the overexpression of miR-107 or silencing of its target, KIF23, markedly suppresses the proliferation, survival, and motility of human and mouse hepatoma cells. In this work, we demonstrate that the disruption of miR-107/Kif23 signaling effectively protects mice from an aggressive form of oncogene-induced liver cancer in vivo, implying that targeting miR-107/KIF23 might be a novel therapeutic approach for hepatocellular carcinoma in humans.