During tumor formation and expansion, increasing glucose metabolism is necessary for unrestricted growth of tumor cells. Expression of key glycolytic enzyme alpha-enolase (ENO1) is controversial and its modulatory mechanisms are still unclear in non-small cell lung cancer (NSCLC). The expression of ENO1 was examined in NSCLC and non-cancerous lung tissues, NSCLC cell lines, and immortalized human bronchial epithelial cell (HBE) by quantitative real-time reverse transcription PCR (qRT-PCR), immunohistochemistry, and Western blot, respectively. The effects and modulatory mechanisms of ENO1 on cell glycolysis, growth, migration, invasion, and in vivo tumorigenesis and metastasis in nude mice were also analyzed. ENO1 expression was increased in NSCLC tissues in comparison to non-cancerous lung tissues. Similarly, NSCLC cell lines A549 and SPCA-1 also express higher ENO1 than HBE cell line in both mRNA and protein levels. Overexpressed ENO1 significantly elevated NSCLC cell glycolysis, proliferation, clone formation, migration, and invasion in vitro, as well as tumorigenesis and metastasis in vivo by regulating the expression of glycolysis, cell cycle, and epithelial-mesenchymal transition (EMT)-associated genes. Conversely, ENO1 knockdown reversed these effects. More importantly, our further study revealed that stably upregulated ENO1 activated FAK/PI3K/AKT and its downstream signals to regulate the glycolysis, cell cycle, and EMT-associated genes. This study showed that ENO1 is responsible for NSCLC proliferation and metastasis; thus, ENO1 might serve as a potential molecular therapeutic target for NSCLC treatment.

Government policy is a major human factor that causes changes in land use. Thus, simulating the dynamics of land-use systems provides important information to support decisions on land management and land-use planning, and to analyze and quantify the consequences of policies. In the present study, we predicted land-use changes and their potential impacts on food security in the environmentally fragile Guyuan District, in the Ningxia Hui Autonomous Region of north-central China, under the influence of a program to convert sloping agricultural land to conservation uses. Baseline and conservation policy scenarios (2005 to 2020) were developed based on input from local stakeholders and expert knowledge. For the baseline and conservation policies, we formulated high-, moderate-, and low-growth scenarios, analyzed the driving mechanisms responsible for the land-use dynamics, and then applied a previously developed "dynamics of land systems" model to simulate changes in land uses based on the driving mechanisms. We found that spatially explicit policies can promote the conversion of land to more sustainable uses; however, decreasing the amount of agricultural and urban land and increasing grassland and forest cover will increase the risk of grain shortages, and the effect will be more severe under the conservation and high-growth scenarios than under the baseline and low-growth scenarios. The Guyuan case study suggests that, during the next decade, important trade-offs between environmental conservation and food security will inevitably occur. Future land-use decisions should carefully consider the balance between land resource conservation, agricultural production, and urban expansion.

Nasopharyngeal carcinoma (NPC) is one of the most common malignant tumors in Chinese and other Southeast Asians. We aimed to explore the precise mechanism for NESG1 in NPC for understanding the pathogenesis of NPC. Transwell, Boyden assays, and wounding healing were respectively performed for cell metastasis. The microRNA (miRNA) microarray and luciferase reporter assays were designed to clarify NESG1-modulated miRNAs and miR-1254-targeted protein. Western blotting assays examined the pathways regulated by miR-1254, the (Hepatoma-Derived Growth Factor) HDGF/DDX5 complex, and NESG1. The chromatin immunoprecipitation (ChIP), electrophoretic mobility shift assay (EMSA), and co-immunoprecipitation (coIP) assays were used to explore the DNA-protein complex and protein-protein complex. NESG1 suppressed NPC migration and invasion via Wnt/β-catenin signaling. Further, miR-1254 was confirmed as a positive downstream modulator of NESG1 reducing metastatic abilities of NPC cells in vivo and in vitro. Transduction of HDGF significantly restored cell migration and invasion ability in miR-1254-overexpressing NPC cells. In clinical samples, miR-1254 expression was negatively correlated with HDGF and positively correlated with NESG1 expression. miR-1254 acts as an independent prognostic factor for NPC, which was induced by NESG1 to suppress NPC metastasis via inactivating Wnt/β-catenin pathway and its downstream EMT signals.

Background: Kinesin family member 23 (KIF23) is recognised as an important tumour promoter involved in the pathogenesis of various cancers. However, its role and underlying molecular mechanisms in regulating cervical cancer (CC) growth and primary chemoresistance remain to be fully elucidated. Methods: The expression and prognostic significance of KIF23 were initially assessed through bioinformatic analyses and subsequently validated in clinical specimens. To evaluate the effects of KIF23 on cell proliferation and cisplatin (DDP) sensitivity in CC cells, in vitro and in vivo experiments were conducted using CRISPR/Cas9 knockout, overexpression and mouse xenograft models. Co‐immunoprecipitation, protein half‐life assays and ubiquitination assays were employed to elucidate the interactions and regulatory mechanisms involving KIF23, myosin heavy chain 9 (MYH9), minichromosome maintenance protein 2 (MCM2) and proliferating cell nuclear antigen (PCNA), thereby revealing the molecular basis of KIF23‐mediated CC progression and primary chemoresistance. Results: KIF23 is highly expressed in CC tissues and is significantly correlated with poor prognosis and DDP resistance in patients. The knockout of KIF23 inhibited cell proliferation, induced G1‐phase arrest and enhanced chemosensitivity to DDP. Mechanistically, the C‐terminal domain of KIF23 was found to directly bind to the myosin tail domain of MYH9. This interaction stabilises MYH9 by recruiting deubiquitinase 7 (ubiquitin‐specific protease 7 [USP7]), which removes K48‐linked ubiquitin chains. The consequent upregulation of MYH9 promoted the recruitment of ubiquitin‐specific protease 15 (USP15) to deubiquitinate MCM2, thereby preventing its degradation. Lysine 469 (K469) of MCM2 was identified as the key site for MYH9‐induced deubiquitination. Furthermore, elevated MCM2 levels enhanced its binding to PCNA, thereby promoting CC cell proliferation. Conclusions: These findings demonstrated that elevated KIF23 levels act as an unfavorable prognostic factor for CC by promoting cell proliferation and primary chemoresistance via the activation of the MYH9/MCM2/PCNA axis. Thus, KIF23 may represent a promising therapeutic target for improving clinical outcomes in CC. Highlights: Cisplatin treatment induces KIF23 expression in a concentration‐ and time‐dependent manner. KIF23 recruits USP7, which removes the K48‐linked ubiquitin chain of MYH9, thereby stabilising MYH9 and facilitating its nuclear transport. MYH9 recruits USP15, thereby stabilising MCM2, which, in turn, regulates the G1/S phase transition by binding to PCNA. Targeting the KIF23/MYH9/MCM2/PCNA axis sensitises cervical cancer cells to cisplatin.