The high mortality rate associated with melanoma primarily results from metastasis and recurrence. However, the precise mechanisms driving these processes remain poorly understood. Intercellular communication between cancer cells and non-cancer cells significantly influences the tumor microenvironment and plays a crucial role in metastasis. Therefore, our current study aims to investigate the role and mechanism of long non-coding RNAs (lncRNAs) in regulating the interaction between melanoma cancer stem cells (CSCs) and non-CSCs during the metastatic colonization process. This study has characterized a novel lncRNA called Gm33149. Importantly, we provide evidence for the first time that Gm33149, originating from highly metastatic melanoma stem cells (OL-SD), can be packaged into exosomes and transferred to low-metastatic nonstem cells (OL). Once internalized by OL cells, Gm33149 exerts its function through a competitive endogenous RNA mechanism (ceRNA) involving miR-5623-3p. Specifically, Gm33149 competitively binds to miR-5623-3p, thereby activating the Wnt signaling pathway and promoting the acquisition of a more aggressive metastatic phenotype by OL cells. In summary, our findings suggest that targeting lncRNA Gm33149 within extracellular vesicles could potentially serve as a therapeutic strategy for the treatment of metastatic melanoma.

与黑色素瘤相关的高死亡率主要是由于转移和复发造成的。然而，驱动这些过程的精确机制仍然知之甚少。癌细胞与非癌细胞之间的细胞间通讯显着影响肿瘤微环境，并在转移中发挥至关重要的作用。因此，我们目前的研究旨在探讨长非编码RNA（lncRNA）在调节黑色素瘤癌症干细胞（CSC）和非CSC在转移定植过程中相互作用的作用和机制。这项研究鉴定了一种名为 Gm33149 的新型 lncRNA。重要的是，我们首次提供证据证明源自高转移性黑色素瘤干细胞（OL-SD）的Gm33149可以被包装到外泌体中并转移到低转移性非干细胞（OL）中。一旦被 OL 细胞内化，Gm33149 通过涉及 miR-5623-3p 的竞争性内源 RNA 机制 (ceRNA) 发挥其功能。具体来说，Gm33149 竞争性地结合 miR-5623-3p，从而激活 Wnt 信号通路并促进 OL 细胞获得更具侵袭性的转移表型。总之，我们的研究结果表明，靶向细胞外囊泡内的 lncRNA Gm33149 可能成为治疗转移性黑色素瘤的一种治疗策略。