Background N6-methyladenosine (m6A) methylation, a well-known modification with new epigenetic functions, has been reported to participate in the tumorigenesis of hepatocellular carcinoma (HCC), providing novel insights into the molecular pathogenesis of this disease. However, as the key component of m6A methylation, Wilms tumor 1-associated protein (WTAP) has not been well studied in HCC. Here we investigated the biological role and underlying mechanism of WTAP in liver cancer. Methods We determined the expression of WTAP and its correlation with clinicopathological features using tissue microarrays and the Cancer Genome Atlas (TCGA) dataset. And we clarified the effects of WTAP on HCC cells using cell proliferation assay, colony formation, Edu assay and subcutaneous xenograft experiments. We then applied RNA sequencing combined with gene expression omnibus (GEO) data to screen candidate targets of WTAP. Finally, we investigated the regulatory mechanism of WTAP in HCC by m6A dot blot assay, methylated RNA immunoprecipitation (MeRIP) assay, dual luciferase reporter assay, RNA immunoprecipitation (RIP) assay and Chromatin immunoprecipitation (ChIP) assay. Results We demonstrated that WTAP was highly expressed in HCC which indicated the poor prognosis, and that WTAP expression served as an independent predictor of HCC survival. Functionally, WTAP promoted the proliferation capability and tumor growth of HCC cells in vitro and in vivo. Furthermore, ETS proto-oncogene 1 (ETS1) was identified as the downstream effector of WTAP. The m6A modification regulated by WTAP led to post-transcriptional suppression of ETS1, with the implication of Hu-Antigen R (HuR) as an RNA stabilizer. Then ETS1 was found to inhibit the progression of HCC and could rescue the phenotype induced by WTAP deficiency. Moreover, WTAP modulated the G2/M phase of HCC cells through a p21/p27-dependent pattern mediated by ETS1. Conclusion We have identified that WTAP is significantly up-regulated in HCC and promotes liver cancer development. WTAP-guided m6A modification contributes to the progression of HCC via the HuR-ETS1-p21/p27 axis. Our study is the first to report that WTAP-mediated m6A methylation has a crucial role in HCC oncogenesis, and highlights WTAP as a potential therapeutic target of HCC treatment. Electronic supplementary material The online version of this article (10.1186/s12943-019-1053-8) contains supplementary material, which is available to authorized users.

Highly efficient four-wave mixing (FWM) and six-wave mixing (SWM) processes can coexist in a four-level Y-type atomic system due to atomic coherence. The simultaneously opened dual electromagnetically induced transparency windows in this four-level atomic system allow observation of these two nonlinear optical processes at the same time, which enables detailed studies of the interplay between the FWM and SWM processes. Three-photon and five-photon destructive interferences are also observed.

Using phase control between four-wave mixing (FWM) and six-wave mixing (SWM) channels in a four-level atomic system, we demonstrate temporal and spatial interferences between these two nonlinear optical processes. Efficient and coexisting FWM and SWM signals are produced in the same electromagnetically induced transparency window via atomic coherence. The temporal interference has a femtosecond time scale corresponding to the optical transition frequency. Such studies of intermixing between different order nonlinear optical processes with a controllable phase delay can have important applications in high-precision measurements, coherence quantum control, and quantum information processing.

Background: N6-methyladenosine (m 6 A) modification is an emerging layer of epigenetic regulation which is widely implicated in the tumorigenicity of hepatocellular carcinoma (HCC), offering a novel perspective for investigating molecular pathogenesis of this disease. The role of AlkB homolog 5 (ALKBH5), one of the m 6 A demethylases, has not been fully explored in HCC. Here we clarify the biological profile and potential mechanisms of ALKBH5 in HCC. Methods: Expression of ALKBH5 and its correlation with clinicopathological characteristics of HCC were evaluated using tissue microarrays and online datasets. And biological effects of ALKBH5 in HCC were determined in vitro and in vivo. Subsequently, methylated RNA immunoprecipitation sequencing (MeRIP-seq) combined with RNA sequencing (RNA-seq), and following m 6 A dot blot, MeRIP-qPCR, RIP-qPCR or dual luciferase reporter assays were employed to screen and validate the candidate targets of ALKBH5. Results: We demonstrated that ALKBH5 was down-regulated in HCC, and decreased ALKBH5 expression was an independent prognostic factor of worse survival in HCC patients. Functionally, ALKBH5 suppressed the proliferation and invasion capabilities of HCC cells in vitro and in vivo. Mechanistically, ALKBH5-mediated m 6 A demethylation led to a post-transcriptional inhibition of LY6/PLAUR Domain Containing 1 (LYPD1), which could be recognized and stabilized by the m 6 A effector IGF2BP1. In addition, we identified that LYPD1 induced oncogenic behaviors of tumors in contrast to ALKBH5. Dysregulation of ALKBH5/LYPD1 axis impelled the progression of HCC. Conclusion: Our study reveals that ALKBH5, characterized as a tumor suppressor, attenuates the expression of LYPD1 via an m 6 A-dependent manner in HCC cells. Our findings enrich the landscape of m 6 A-modulated tumor malignancy, and provide new insights into potential biomarkers and therapeutic targets of HCC treatment.

We demonstrate a novel type of stable multicomponent vector solitons consisting of two perpendicular four-wave mixing (FWM) dipole components induced by electromagnetically induced gratings. We analyze the formation and steering of the steady dipole solitons and their dynamical (energy transfer) effects. The dipole-mode solitons of two FWM processes have horizontal and vertical orientations, respectively. Omnidirectional Bragg reflections are also investigated.

Radiative lifetimes of high quality Mn:ZnSe nanocrystals synthesized by nucleation-doping method are experimentally measured at wavelength near 580 nm. The slow decay rate in millisecond time scale is identified as the radiative decay from the 4 T 1 metastable excited state of Mn 2+ ions embedded in the ZnSe nanocrystals. Also, two fast decay components are measured at this wavelength with much lower intensities, which can be attributed to the emission tails from the host ZnSe nanocrystals and from the surface-trap states or the self-activated luminescence due to Mn ion pairs, respectively. Size dependences of the radiative decay rates for the Mn:ZnSe samples are measured.

We study three ͑nested, parallel, and sequential cascade͒ types of schemes for doubly dressed four-wavemixing processes in an open five-level atomic system. The interaction between two dressing fields of the nested-cascade scheme is strongest and weakest for the parallel-cascade scheme, with the sequential scheme intermediate between them. Mutual-dressing processes and constructive or destructive interference between two coexisting dressed multiwave mixing channels in such a system are also considered. Investigations of these multidressing mechanisms and interactions are very useful to understand and control the generated high-order nonlinear optical signals.

Hepatocellular carcinoma (HCC) is a highly heterogeneous, multigene-driven malignant tumor. Long chain acyl-CoA synthetase 4 (ACSL4), an enzyme has pivotal roles in arachidonic acid (AA) metabolism. However, its function and the underlying molecular mechanisms in HCC are still not fully elucidated. Here, we identified ACSL4 as a novel marker for AFP high subtype HCC through transcriptome profiling. ACSL4 was frequently upregulated in HCC samples and associated with poor prognosis. Functionally, ACSL4 knockdown resulted in decreased cell growth, whereas ectopic ACSL4 expression facilitated tumor formation in vitro and in vivo. Mechanistically, ACSL4 stabilized the oncoprotein c-Myc through ubiquitin-proteasome system in an ERK/FBW7-dependent manner. Cell growth ability mediated by ACSL4 elevation was partly attenuated by c-Myc depletion using siRNA or its inhibitor 10058-F4. In contrast, the effects of ACSL4 silencing were partially reversed by c-Myc overexpression via FBW7 knockdown. Clinically, ACSL4 expression was positively correlated with c-Myc in HCC. In conclusion, ACSL4 is a novel marker for AFP high subtype HCC. Our data uncovered a new mechanism by which ACSL4 promotes HCC progression via c-Myc stability mediated by ERK/ FBW7/c-Myc axis and could be a valuable prognostic biomarker and a potential therapeutic target in HCC.