KLF5 regulates actin remodeling to enhance the metastasis of nasopharyngeal carcinoma.

Transcription factors (TFs) engage in various cellular essential processes including differentiation, growth and migration. However, the master TF involved in distant metastasis of nasopharyngeal carcinoma (NPC) remains largely unclear. Here we show that KLF5 regulates actin remodeling to enhance NPC metastasis. We analyzed the msVIPER algorithm-generated transcriptional regulatory networks and identified KLF5 as a master TF of metastatic NPC linked to poor clinical outcomes. KLF5 regulates actin remodeling and lamellipodia formation to promote the metastasis of NPC cells in vitro and in vivo. Mechanistically, KLF5 preferentially occupies distal enhancer regions of ACTN4 to activate its transcription, whereby decoding the informative DNA sequences. ACTN4, extensively localized within actin cytoskeleton, facilitates dense and branched actin networks and lamellipodia formation at the cell leading edge, empowering cells to migrate faster. Collectively, our findings reveal that KLF5 controls robust transcription program of ACTN4 to modulate actin remodeling and augment cell motility which enhances NPC metastasis, and provide new potential biomarkers and therapeutic interventions for NPC.

Effect of an educational video about ERAS on reducing preoperative anxiety and promoting recovery.

Video propaganda is reported effectively improving patients' understanding of operation. However, whether a video introducing patients' most concerns can reduce preoperative anxiety and promote recovery stays unsealed. In this study, we investigated the effects of complementary therapy of educational video during preoperative visit. The results showed that thirty-five (23.2%) parents in Group Control were diagnosed as anxiety according to SAS, and nineteen (12.3%) patients were diagnosed after video intervention. The APAIs anxiety score and APAIs information score in Group Video were lower than those in Group Control. Compared with Group Control, video visit helped to increase the first-attempt pass rate of the knowledge retention exam and solve the patient's most worried concerns, and decrease incidence of emergence agitation, total cost of hospitalization and length of hospital stay. Moreover, video visit improved satisfaction degrees of patients and their main family members. Briefly, our study demonstrated video visit can improve patients' knowledge of anesthesia and decrease their preoperative anxiety, which may represent an important complementary therapy to routine preoperative visits.

VIRMA promotes nasopharyngeal carcinoma, tumorigenesis, and metastasis by upregulation of E2F7 in an m6A-dependent manner.

The N6-methyladenosine (m6A) modification possesses new and essential roles in tumor initiation and progression by regulating mRNA biology. However, the role of aberrant m6A regulation in nasopharyngeal carcinoma (NPC) remains unclear. Here, through comprehensive analyses of NPC cohorts from the GEO database and our internal cohort, we identified that VIRMA, an m6A writer, is significantly upregulated in NPC and plays an essential role in tumorigenesis and metastasis of NPC, both in vitro and in vivo. High VIRMA expression served as a prognostic biomarker and was associated with poor outcomes in patients with NPC. Mechanistically, VIRMA mediated the m6A methylation of E2F7 3'-UTR, then IGF2BP2 bound, and maintained the stability of E2F7 mRNA. An integrative high-throughput sequencing approach revealed that E2F7 drives a unique transcriptome distinct from the classical E2F family in NPC, which functioned as an oncogenic transcriptional activator. E2F7 cooperated with CBFB-recruited RUNX1 in a non-canonical manner to transactivate ITGA2, ITGA5, and NTRK1, strengthening Akt signaling-induced tumor-promoting effect.

WTAP-mediated m6A modification of lncRNA DIAPH1-AS1 enhances its stability to facilitate nasopharyngeal carcinoma growth and metastasis.

As the most predominant RNA epigenetic regulation in eukaryotic cells, N6-methyladenosine (m6A) plays a critical role in human tumorigenesis and cancer progression. However, the biological function and molecular mechanism of m6A regulation in naso-pharyngeal carcinoma (NPC) remain elusive. Here, we showed that Wilms' tumor 1-associating protein (WTAP) expression was apparently upregulated in NPC, and increased WTAP was associated with poor prognosis. WTAP upregulated in NPC was fine-tuned by KAT3A-mediated H3K27 acetylation. Functionally, WTAP was required for the growth and metastasis of NPC. Mechanistically, lncRNA DIAPH1-AS1 was identified as a bona fide m6A target of WTAP. WTAP-mediated m6A modification of DIAPH1-AS1 enhanced its stability relying on the m6A reader IGF2BP2-dependent pathway. Furthermore, DIAPH1-AS1 acted as a molecular adaptor that promoted MTDH-LASP1 complex formation and upregulated LASP1 expression, ultimately facilitating NPC growth and metastasis. Thus, WTAP-mediated DIAPH1-AS1 m6A methylation is required for NPC tumorigenesis and metastasis.

Histone deacetylase inhibitors differentially regulate c-Myc expression in retinoblastoma cells.

Retinoblastoma (RB) is the most prevalent childhood intraocular cancer type. Previous studies have demonstrated that c-myc (a proto-oncogene) is associated with tumorigenesis. However, at present, the influence of the expression profile and bioactivity of c-Myc on RB occurrence and progression is yet to be characterised. Notably, the present study demonstrated that c-myc is downregulated in the RB cell line WERI-Rb1. However, treatment with the histone deacetylase (HDAC) inhibitor trichostatin A (TSA) was revealed to significantly upregulate the expression of c-Myc mRNA and protein in WERI-Rb1 cells. Moreover, TSA increased the activity of the c-myc promoter in WERI-Rb1 cells, and the expression of c-Myc was also regulated by other HDAC inhibitors, including vorinostat (SAHA), valproic acid sodium salt (VPA) and entinostat. Notably, although c-myc was silenced in the Y79 cell line, the HDAC inhibitor TSA did not induce upregulation of mRNA and protein in Y79 cells. By contrast, certain HDAC inhibitors (TSA, VPA and SAHA) were discovered to significantly decrease the activity of the c-myc promoter in Y79 cells. Furthermore, the current data indicated that exogenous c-myc expression has a mild inhibitory effect on WERI-Rb1 and Y79 cell viability. Therefore, the present study revealed novel insights into the expression mechanism and bioactivity of c-Myc in RB cells.

Retinal Neuron Is More Sensitive to Blue Light-Induced Damage than Glia Cell Due to DNA Double-Strand Breaks.

Blue light is a major component of visible light and digital displays. Over-exposure to blue light could cause retinal damage. However, the mechanism of its damage is not well defined. Here, we demonstrate that blue light (900 lux) impairs cell viability and induces cell apoptosis in retinal neurocytes in vitro. A DNA electrophoresis assay shows severe DNA damage in retinal neurocytes at 2 h after blue light treatment. γ-H2AX foci, a specific marker of DNA double-strand breaks (DSBs), is mainly located in the Map2-posotive neuron other than the glia cell. After assaying the expression level of proteins related to DNA repair, Mre11, Ligase IV and Ku80, we find that Ku80 is up-regulated in retinal neurocytes after blue light treatment. Interestingly, Ku80 is mainly expressed in glia fibrillary acidic protein (GFAP)-positive glia cells. Moreover, following blue light exposure in vivo, DNA DSBs are shown in the ganglion cell layer and only observed in Map2-positive cells. Furthermore, long-term blue light exposure significantly thinned the retina in vivo. Our findings demonstrate that blue light induces DNA DSBs in retinal neurons, and the damage is more pronounced compared to glia cells. Thus, this study provides new insights into the mechanisms of the effect of blue light on the retina.