Yihao Sun

Abstract 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.

Significance Cancer is the leading cause of death worldwide, although studies revealed that dysregulation of the Hippo pathway contributes to tumorigenesis, whereas its roles in tumor invasion and cell migration remain paradoxical and largely elusive. Using Drosophila as a model, we herein find cross-talk between the Hippo and JNK pathways in regulating cell migration and invasion. Mechanistically, we identify bantam -Rox8 modules as essential components downstream of Yorkie in mediating JNK-dependent cell invasion. Our finding is particularly important as it offers a wake-up call for therapeutic interventions of Hippo-related cancers, because simply increasing Hippo signal activity may paradoxically accelerate cell invasion and metastasis.

BACKGROUND: Alleviating arsenic (As) contamination is a high-priority environmental issue. Hyperaccumulator plants may harbor endophytic bacteria able to detoxify As. Therefore, we investigated the distribution, diversity, As (III) resistance levels, and resistance-related functional genes of arsenite-resistant bacterial endophytes in Pteris vittata L. growing in a lead-zinc mining area with different As contamination levels. RESULTS: A total of 116 arsenite-resistant bacteria were isolated from roots of P. vittata with different As concentrations. Based on the 16S rRNA gene sequence analysis of representative isolates, the isolates belonged to Proteobacteria, Actinobacteria, and Firmicutes. Major genera found were Agrobacterium, Stenotrophomonas, Pseudomonas, Rhodococcus, and Bacillus. The most highly arsenite-resistant bacteria (minimum inhibitory concentration > 45 mM) were isolated from P. vittata with high As concentrations and belonged to the genera Agrobacterium and Bacillus. The strains with high As tolerance also showed high levels of indole-3-acetic acid (IAA) production and carried arsB/ACR3(2) genes. The arsB and ACR3(2) were most likely horizontally transferred among the strains. CONCLUSION: The results of this study suggest that P. vittata plants with high As concentrations may select diverse arsenite-resistant bacteria; this diversity might, at least partly, be a result of horizontal gene transfer. These diverse endophytic bacteria are potential candidates to enhance phytoremediation techniques.

Abstract The c-Jun N-terminal kinase (JNK) pathway plays essential roles in regulating a variety of physiological processes including cell migration and invasion. To identify critical factors that regulate JNK-dependent cell migration, we carried out a genetic screen in Drosophila based on the loss-of-cell polarity-triggered cell migration in the wing epithelia, and identified MKK3 licorne ( lic ) as an essential regulator of JNK-mediated cell migration and invasion. We found that loss of lic suppressed ptc > scrib-IR or ptc > Egr triggered cell migration in the wing epithelia, and Ras v12 /lgl −/− induced tumor invasion in the eye discs. In addition, ectopic expression of Lic is sufficient to induce JNK-mediated but p38-independent cell migration, and cooperate with oncogenic Ras to promote tumor invasion. Consistently, Lic is able to activate JNK signaling by phosphorylating JNK, which up-regulates the matrix metalloproteinase MMP1 and integrin, characteristics of epithelial–mesenchymal transition (EMT). Moreover, lic is required for physiological JNK-mediate cell migration in thorax development. Finally, expression of human MKK3 in Drosophila is able to initiate JNK-mediated cell migration, cooperates with oncogenic Ras to trigger tumor invasion, and rescue loss-of- lic induced thorax closure defect. As previous studies suggest that MKK3 specifically phosphorylates and activates p38MAPK, our data provide the first in vivo evidence that MKK3 regulates JNK-dependent cell migration and invasion, a process evolutionarily conserved from flies to human.