N6-methyladenosine modification of REG1α facilitates colorectal cancer progression via ß-catenin/MYC/LDHA axis mediated glycolytic reprogramming.

Aerobic glycolysis has been considered as a hallmark of colorectal cancer (CRC). However, the potential functional regulators of glycolysis in CRC remains to be elucidated. In the current study, we found that Regenerating islet-derived protein 1-alpha (REG1α) was significantly increased in both CRC tissues and serum, and positively associated with CRC patients' lymph node metastasis, advanced tumor stage, and unfavorable prognosis. Ectopic expression of REG1α contributed to various tumorigenic properties, including cell proliferation, cell cycle, migration, invasion, and glycolysis. In contrast, REG1α deficiency in CRC cells attenuated malignant properties and glucose metabolism. Mechanically, REG1α promoted CRC proliferation and metastasis via ß-catenin/MYC axis-mediated glycolysis upregulation. Moreover, the malignant behaviors governed by REG1α could be effectively abolished by silencing of Wnt/ß-catenin/MYC axis or glycolysis process using specific inhibitors. Besides, REG1α expression was mediated by METTL3 in an m6A-dependent manner. Overall, our work defines a novel regulatory model of the METTL3/REG1α/ß-catenin/MYC axis in CRC, which indicates that REG1α could function as a novel biomarker and a potential therapeutic target for patients with CRC.

Spatial and Temporal Patterns of Ecological Connectivity in the Ethnic Areas, Sichuan Province, China.

With ongoing economic and social development, natural habitats are becoming increasingly fragmented, blocking habitat connections and reducing landscape connectivity. The study of changes in ecological connectivity can provide valuable information for habitat and landscape restoration, which are necessary for sustainable regional development. Despite the growing interest in this issue, studies that reveal the change in ecological connectivity in the compounded areas of ecological vulnerability and deep poverty are still lacking. In this paper, one of the most underdeveloped and ecologically fragile southwestern ethnic regions of China, the Sanzhou region of Sichuan Province, was the study area. Based on a vector map of current land-use status and vector data on ecosystem factors and nature reserves in 2010 and 2015, the change in ecological connectivity was analyzed using the minimum cumulative resistance model using GIS spatial analysis method. Firstly, ecological sources were identified based on the distribution of ecological functional areas. Secondly, the ecological resistance surface based on ecosystem service value is revised by integrating the three dimensions of topography and hydrology, ecological environment and development, and utilization intensity. Finally, the ecological connectivity of ethnic areas in southwest China in 2010 and 2015 was compared and analyzed through the perspective of ecological resistance. The results show that: (1) From 2010 to 2015, the overall ecological connectivity decreased. (2) There were six areas of high ecological resistance featuring human activity and ecological degradation: the Anning River Valley in Liangshan Prefecture, Ganzi, Dege and Luho counties in Ganzi Prefecture, and Ruoergai and Hongyuan counties in Aba Prefecture. (3) Low ecological resistance areas were more numerous and widely distributed, forming an ecological protection barrier for the three autonomous prefectures, and regulating and protecting their natural environments. It is necessary to maintain and strengthen this protection; accordingly, measures are proposed to improve ecological connectivity. This study provides a reference for achieving ecological security and harmonious coexistence between humans and nature in this region.