Epigenetic dysregulation is a common feature of a myriad of human diseases, particularly cancer. Defining the epigenetic defects associated with malignant tumors has become a focus of cancer research resulting in the gradual elucidation of cancer cell epigenetic regulation. In fact, most stages of tumor progression, including tumorigenesis, promotion, progression, and recurrence are accompanied by epigenetic alterations, some of which can be reversed by epigenetic drugs. The main objective of epigenetic therapy in the era of personalized precision medicine is to detect cancer biomarkers to improve risk assessment, diagnosis, and targeted treatment interventions. Rapid technological advancements streamlining the characterization of molecular epigenetic changes associated with cancers have propelled epigenetic drug research and development. This review summarizes the main mechanisms of epigenetic dysregulation and discusses past and present examples of epigenetic inhibitors in cancer diagnosis and treatment, with an emphasis on the development of epigenetic enzyme inhibitors or drugs. In the final part, the prospect of precise diagnosis and treatment is considered based on a better understanding of epigenetic abnormalities in cancer.

Three-dimensional (3D) genomics is the frontier field in the post-genomics era, its foremost content is the relationship between chromatin spatial conformation and regulation of gene transcription. Cancer biology is a complex system resulting from genetic alterations in key tumor oncogenes and suppressor genes for cell proliferation, DNA replication, cell differentiation, and homeostatic functions. Although scientific research in recent decades has revealed how the genome sequence is mutated in many cancers, high-order chromosomal structures involved in the development and fate of cancer cells represent a crucial but rarely explored aspect of cancer genomics. Hence, dissection of the 3D genome conformation of cancer helps understand the unique epigenetic patterns and gene regulation processes that distinguish cancer biology from normal physiological states. In recent years, research in tumor 3D genomics has grown quickly. With the rapid progress of 3D genomics technology, we can now better determine the relationship between cancer pathogenesis and the chromatin structure of cancer cells. It is becoming increasingly explicit that changes in 3D chromatin structure play a vital role in controlling oncogene transcription. This review focuses on the relationships between tumor gene expression regulation, tumor 3D chromatin structure, and cancer phenotypic plasticity. Furthermore, based on the functional consequences of spatial disorganization in the cancer genome, we look forward to the clinical application prospects of 3D genomic biomarkers.

Objectives: The evolutionary conserved JNK pathway plays crucial role in cell death, yet factors that modulate this signalling have not been fully disclosed. In this study, we aim to identify additional factors that regulate JNK signalling in cell death, and characterize the underlying mechanisms.Materials and Methods: Drosophila were raised on standard media, and cross was carried out at 25°C. The Gal4/UAS system was used to express proteins or RNAi in a specific temporal and spatial pattern. Gene expression was revealed by GFP fluorescence, X‐gal staining or immunostaining of 3rd instar larval eye and wing discs. Cell death was visualized by acridine orange (AO) staining. Images of fly eyes and wings were taken by OLYMPUS microscopes.Results: We found that licorne (lic) encoding the Drosophila MKK3 is an essential regulator of JNK‐mediated cell death. Firstly, loss of lic suppressed ectopic Egr‐triggered JNK activation and cell death in eye and wing development. Secondary, lic is necessary for loss‐of‐cell polarity‐induced, physiological JNK‐dependent cell death in wing development. Thirdly, Lic overexpression is sufficient to initiate JNK‐mediated cell death in developing eyes and wings. Furthermore, ectopic Lic activates JNK signalling by promoting JNK phosphorylation. Finally, genetic epistatic analysis confirmed that Lic acts in parallel with Hep in the Egr‐JNK pathway.Conclusions: This study not only identified Lic as a novel component of the JNK signalling, but also disclosed the crucial roles and mechanism of Lic in cell death.

P63 plays a crucial role in epithelia-originating tumours; however, its role in intrahepatic cholangiocarcinoma (iCCA) has not been completely explored. Our study revealed the oncogenic properties of p63 in iCCA and identified the major expressed isoform as ΔNp63α. We collected iCCA clinical data from The Cancer Genome Atlas database and analyzed p63 expression in iCCA tissue samples. We further established genetically modified iCCA cell lines in which p63 was overexpressed or knocked down to study the protein function/function of p63 in iCCA. We found that cells overexpressing p63, but not p63 knockdown counterparts, displayed increased proliferation, migration, and invasion. Transcriptome analysis showed that p63 altered the iCCA transcriptome, particularly by affecting cell adhesion-related genes. Moreover, chromatin accessibility decreased at p63 target sites when p63 binding was lost and increased when p63 binding was gained. The majority of the p63 bound sites were located in the distal intergenic regions and showed strong enhancer marks; however, active histone modifications around the Transcription Start Site changed as p63 expression changed. We also detected an interaction between p63 and the chromatin structural protein YY1. Taken together, our results suggest an oncogenic role for p63 in iCCA.

Hepatocellular carcinoma (HCC) accounts for approximately 90% of all primary liver cancers and is one of the main malignant tumor types globally. It is essential to develop rapid, ultrasensitive, and accurate strategies for the diagnosis and surveillance of HCC. In recent years, aptasensors have attracted particular attention owing to their high sensitivity, excellent selectivity, and low production costs. Optical analysis, as a potential analytical tool, offers the advantages of a wide range of targets, rapid response, and simple instrumentation. In this review, recent progress in several types of optical aptasensors for biomarkers in early diagnosis and prognosis monitoring of HCC is summarized. Furthermore, we evaluate the strengths and limitations of these sensors and discuss the challenges and future perspectives for their use in HCC diagnosis and surveillance.

Circadian rhythms regulate various biological processes, such as cell division and metabolism. Circadian rhythm disruption (CRD) is often associated with malignant tumor progression and poor prognosis. However, the effect of CRD on liver cancer prognosis has not been systematically analyzed or fully elucidated. Here, we developed a method to quantify and assess intratumoral CRD in a single-cell transcriptomic analysis of liver cancer and systematically analyzed the role of CRD in tumor progression and prognosis. Furthermore, a LASSO-Cox regression model based on 14 CRD genes was used to predict overall patient survival across multiple datasets. We found that malignant cells with high CRD scores were enriched in specific metabolic pathways, such as fatty acid metabolism and the trichloroacetic acid cycle. Intercellular communication analysis suggested that CRD regulates chemokine-mediated interactions. With the bulk transcriptomic datasets, we determined that LiverCRD scores were significantly correlated with macrophage infiltration levels and could guide targeted immunotherapy and chemotherapy strategies. In addition, LiverCRD is also associated with the mutational landscape—for example, TP53 mutation frequency was higher in high-CRD samples. Finally, the 14-gene-based LASSO-Cox regression model could accurately predict overall patient survival across datasets. In conclusion, Our proposed analysis reflects the relationship between CRD and the immune environment in liver cancer, suggesting that CRD may serve as a potential prognostic indicator. Our results may help guide targeted anti-tumor strategies.