Background Esophageal Squamous Cell Carcinoma (ESCC) was characterized as a regional-prevalent and aggressive tumor with high morbidity and mortality. NIMA-related kinase 2 (NEK2) is an interesting oncogene, the alteration of which leads to patients-beneficial outcomes. We aimed to explore the role of NEK2 in ESCC and excavate its mechanism. Methods RNA-seq data were downloaded from TCGA and GEO and analyzed by R software. The protein levels were detected by immunohistochemistry (IHC) or western blot (WB), and mRNA expression was detected by qRT-PCR. The in vitro role of proliferation and migration was detected by Transwell migration assay and by colony formation assay, respectively. The in vivo roles were explored using a subcutaneous xenograft tumor model, where immunofluorescence (IF) and IHC were employed to investigate expression and localization. The interaction between proteins was detected by immunoprecipitation. The stability of proteins was measured by WB in the presence of cycloheximide. Results A higher level of NEK2 was found in ESCC than normal esophageal epithelia in GEO, TCGA, and tissue microarray, which was associated with worse prognoses. The NEK2 knockdown impaired the proliferation and migration of ESCC, which also downregulated YAP1 and EMT markers like N-cadherin and Vimentin in vitro. On the contrary, NEK2 overexpression enhanced the migration of ESCC and elevated the levels of YAP1, N-cadherin, and Vimentin. Additionally, the overexpression of YAP1 in NEK2 knocked down ESCCs partly rescued the corresponding decrease in migration. The knockdown of NEK2 played an anti-tumor role in vivo and was accompanied by a lower level and nucleus shuffling of YAP1. In mechanism, NEK2 interacted with YAP1 and increased the stability of both endogenous and exogenous YAP1 by preventing ubiquitination. Moreover, the computer-predicted phosphorylation site of YAP1, Thr-143, reduced the ubiquitination of HA-YAP1, strengthened its stability, and thus influenced the migration in vitro. Conclusions NEK2 is a prognostic oncogene highly expressed in ESCC and promotes the progression of ESCC in vitro and in vivo. Mechanistically, NEK2-mediated phosphorylation of YAP1 at Thr-143 protects it from proteasome degradation and might serve as a promising therapeutic target in ESCC.

The first principles calculations were performed to investigate site preferences of the alloying elements M (Ti, Nb) doping in Ni3Al, elastic properties and the electronic structure of Ni3Al and Ni3Al-M with the Cambridge sequential total energy package (CASTEP). It was found that M were preferred to replace the Al sites. As the M doping. The bulk, shear and Young's modulus increased and the bulk/shear modulus ratios (B/G) decreased in Ni3Al polycrystalline alloy. While B/G of all alloys were larger than 1.75, signifying that Ni3Al, Ni24Al7Nb and Ni24Al7Ti polycrystalline alloys possessed ductility. Analyzing the electronic structure of Ni3Al and Ni3Al-M, the results showed that the main interaction between the Ni atoms and the Al atoms was covalence in the Ni3Al, after doping elements M (Ti, Nb) in Ni3Al, there was strong orbital hybridization between the Al-3p orbital, Ni-3d orbital and M-d (Ti-3d, Nb-4d) orbital, the covalent bonds between alloying atoms M (Ti, Nb) and their neighbor atoms Ni were stronger than that between Al atom and Ni atom.

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