Novel lncRNA Gm33149 modulates metastatic heterogeneity in melanoma by regulating the miR-5623-3p/Wnt axis via exosomal transfer

作者全名："Chen, Yan; Zhang, Yu-Han; Li, Jie; Shi, Lei; Xie, Jia-Cheng; Han, Xue; Chen, Yu-Ting; Xiang, Meng; Li, Bo-Wen; Xing, H. Rosie; Wang, Jian-Yu"

作者地址："[Chen, Yan; Zhang, Yu-Han; Shi, Lei; Xie, Jia-Cheng; Chen, Yu-Ting; Xiang, Meng; Li, Bo-Wen; Xing, H. Rosie] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China; [Chen, Yan; Zhang, Yu-Han; Shi, Lei; Xie, Jia-Cheng; Chen, Yu-Ting; Xiang, Meng; Li, Bo-Wen; Xing, H. Rosie] Chongqing Med Univ, Chongqing Key Lab Biomed Engn, Chongqing 400016, Peoples R China; [Li, Jie; Han, Xue; Wang, Jian-Yu] Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China"

通信作者："Xing, HR (通讯作者)，Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China.; Xing, HR (通讯作者)，Chongqing Med Univ, Chongqing Key Lab Biomed Engn, Chongqing 400016, Peoples R China.; Wang, JY (通讯作者)，Chongqing Med Univ, Inst Life Sci, Chongqing, Peoples R China."

来源：CANCER GENE THERAPY

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001121283100004

JCR分区：Q1

影响因子：6.4

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：　

摘要："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.Schematic representation of the mechanisms underlying the pro-metastatic activity of lncRNA Gm33149 mediated by exosomal transfer. The figure illustrates the key mechanisms involved in the pro-metastatic activity of lncRNA Gm33149 through exosomal transfer. Melanoma stem cells (OLSD) release exosomes containing lncRNA Gm33149. These exosomes are taken up by non-stem melanoma cells (OL), delivering lncRNA Gm33149 to the recipient cells. Within OL cells, lncRNA Gm33149 functions as a competitive endogenous RNA (ceRNA), sequestering miR-5623-3p. This sequestration prevents miR-5623-3p from binding to its target genes, thereby activating the Wnt signaling pathway. The activated Wnt signaling pathway enhances the migration, invasion, and metastatic colonization capabilities of OL cells. The transfer of lncRNA Gm33149 via exosomes contributes to OL cells acquiring ""metastatic competency"" while promoting their metastatic colonization. These findings underscore the importance of lncRNA Gm33149 in intercellular communication and the metastatic progression of melanoma."

基金机构："National Natural Science Fund [82073277, 82173247]; Science and Technology Project [KJQN202100404]; Project of Chongqing Natural Science Foundation Innovation and Development Fund (Municipal Education Commission) [CSTB2022NS CQ-LZX0023]"

基金资助正文："This work was supported by the National Natural Science Fund (Grant No. 82073277 and 82173247), the Science and Technology Project Affiliated to the EducationDepartment of Chongqing (Grant No. KJQN202100404), and Project of Chongqing Natural Science Foundation Innovation and Development Fund (Municipal Education Commission) (Grant No. CSTB2022NS CQ-LZX0023)."