Protein secretion and extracellular vesicles represent distinct mechanisms through which cancer cells and stromal cells interact to modify the tumor microenvironment. However, most studies on these mechanisms have predominantly focused on elucidating the impact of cancer cells on stromal cells, leaving the interactions between cancer cells and adjacent cancer cells relatively unexplored. We utilized a heterogeneous melanoma metastasis cell model that our laboratory previously developed, comprising POL (Polymetastatic) cells with high metastatic potential and OL (Oligometastatic) cells with low metastatic potential. We applied bioinformatics methods to investigate this model. Our findings reveal that POL cells can secrete exosome-encapsulated miRNA-3184-3p into OL cells. Subsequently, this process targets and inhibits the Nlk gene, activating the Wnt/β-catenin signaling pathway, ultimately promoting the secretion of S100A11 protein by OL cells into the tumor microenvironment. Upon internalization by POL cells, S100A11 further enhances their metastatic capabilities, increasing the intracellular and exosomal content of miRNA-3184-3p. Consequently, a positive feedback loop is established between POL and OL cells, resulting in the continuous malignant progression of the tumor. These findings provide valuable insights into melanoma cell interactions and propose new therapeutic strategies for targeting melanoma metastasis.
Local leisure events satisfy personalized needs and boost local tourism vitality. However, research on leisure event preference recommendations remains inadequate. Event-Based Social Networks (EBSNs) combine online social and offline interactions, but users face information overload, requiring efficient recommendation systems. Current systems face two key challenges: cold-start problems for new users/events and data sparsity. Research shows social relationships help mitigate cold-start issues, while users' interests and social connections change over time, with recent behaviors being more predictive than long-term ones-a fact often overlooked. To address these issues, we propose ERDGAT, a dynamic graph attention network model for event recommendations in EBSNs. The model extracts event features, mines user preferences from historical events, models social relationships using graph attention networks, and captures recent preference features through temporal social networks with long short-term memory networks. Experiments on the Douban Events dataset demonstrate ERDGAT significantly outperforms baseline methods in recommendation accuracy and cold-start mitigation, improving NDCG@10 by 26.5%.
Background: The high mortality rate of lung cancer is largely attributed to metastasis. Lung cancer stem cells (CSC) are conducive to cancer heterogeneity. Long noncoding RNAs are known to participate in various biological processes regulating the development of lung cancer. However, characterization of the role and mechanisms of lncRNA in lung cancer metastasis remains a challenge.Results: We demonstrate that ROLLCSC, a highly expressed lncRNA in LLC-SDs, promotes the metastasis of the low metastatic LLCs both in vitro and in vivo. ROLLCSC can be transferred from LLC-SD to LLC through encapsulation in extracellular vesicles (EVs), ultimately leading to the enhancement of the metastatic phenotype of LLCs. Mechanistically, we demonstrate that the pro-metastatic activity of ROLLCSC is achieved through its function as a competing endogenous RNA (ceRNA) of miR-5623-3p and miR-217-5p to stimulate lipid metabolism.Conclusion: In this study, we have characterized ROLLCSC, a novel lncRNA, as a pivotal regulator in the metastasis of lung cancer, highlighting its potential as a therapeutic target. Specifically, we show that ROLLCSC is encapsulated by the EVs of LLC-SDs and transmitted to the LLCs, where it acts as a ceRNA of miR-5623-3p and miR-217-5p to stimulate lipid metabolism and ultimately augments metastatic colonization of LLCs.
The common pool resource (CPR) theory has inspired the recognition of community self-governance in natural resource management. However, many CPR literature treated government as an external variable to community, without sufficiently considering the close interaction between the two, especially in strong-government context. In this paper, we applied two case villages on the Qinghai-Tibet Plateau of China with different governance systems for caterpillar fungus (Ophiocordyceps sinensis), a CPR with lucrative values, to study the effects of the different government interventions on the local social conditions and rangeland ecosystem. One village interacted with facilitative local government that helped to develop a pro-community self-governance institution, while the other faced a forceful government that substituted the community self-governance. Furthermore, we explored the underlying mechanism from the view of the congruence between the government actions to achieve administrative objectives and the community demands for self-governance. We found that the better outcomes occurred in the village with the facilitative government involvement, because the government actions were congruent with the community demands. The model with facilitative government involvement presents a possible approach, when CPR appropriator boundary became semi-opened to outsiders, by which the community self-governance institution could function well with government help in institution design, monitoring and sanction. Our findings enrich the applications of CPR governance theory, particularly in the aspect that how government-community interacts to develop a self-governance institution in strong-government context.
Despite the unprecedented advancement of cancer treatment, the prognosis for patients with metastatic stage of cancer remains poor. The challenge that underlines this clinical dilemma is the complexity of metastasis. The conventional experiment-driven discovery approaches (the "wet lab") yield overly simplified one-to-one mechanistic relationships that are inept of elucidating the complexity of metastasis. Metastasis research also suffers from the knowledge and skill deficiency of the individual investigators. The importance of the present study is the demonstration that the "dry-lab-driven discovery and wet-lab validation" approach can improve the efficiency of studying complex biological behaviors, and can yield more reliable, objective and comprehensive mechanistic findings that are have clinical significance. Specifically, we applied this approach to study the mechanisms that underline the involvement of exosomal miRNAs in transferring the metastatic capability between heterogenous melanoma cancer cells. We show that the highly metastatic melanoma tumor cells (POL) can transfer their metastatic competency to the low-metastatic melanoma tumor cells (OL) by exosomal miR-211-5p. The oncogenic activity of miR-211-5p is mediated by the target gene guanine nucleotide-binding protein subunit alpha-15 (GNA15) through modifying the immune function of the tumor microenvironment extrinsically; as well as through inhibiting pyroptosis and augmenting glycolysis within OL cells intrinsically. In addition, we show that exosomal sorting of miR-211-5p is like selective and is subjected to regulation by a transcriptional feedback loop between miR-211-5p and zinc finger FYVE-type containing 26 (ZFYVE26). Furthermore, the "8-genes pyroptosis Risk model" derived from LASSO regression analysis was verified as an independent prognostic factor for melanoma.
