YY1-induced lncRNA00511 promotes melanoma progression via the miR-150- 5p/ADAM19 axis

Abstract

AbstractBackground Long noncoding RNAs (lncRNAs) are key regulators of oncogenic processes, and one such lncRNA is lncRNA511 (LINC00511), which is associated with breast, stomach, lung, and colorectal cancers. However, its specific involvement in melanoma remains unclear. Here, we aimed to investigate the expression and functional role of LINC00511 in melanoma. Methods We examined the expression of LINC00511 in melanoma cell lines (A375 and SK-Mel-28) and melanoma tissues obtained from patients. We conducted knockdown experiments to assess the effects of LINC00511 on melanoma cell migration, invasion, and tumor growthin vivo. To investigate LINC00511 transcription regulators, we performed chromatin immunoprecipitation assays. Additionally, we analyzed the subcellular localization of LINC00511 and confirmed that its interaction with microRNA-150-5p (miR-150-5p) by RNA immunoprecipitation assay (RIP), miRNA pull-down and luciferase reporter assay. Furthermore, we conducted rescue assays to validate our findings, namely on the LINC00511/miR-150-5p/ADAM19 axis and its impact on the PI3K/AKT pathway. Results LINC00511 was found to be highly expressed in melanoma cell lines and patient tissues. Knockdown of LINC00511 resulted in the inhibition of melanoma cell migration, invasion, and subcutaneous tumor growthin vivo. Yin Yang 1 (YY1) was identified as the transcription factor responsible for LINC00511 upregulation. Furthermore, LINC00511 was predominantly localized in the cytoplasm and exhibited direct interaction with miR-150-5p. Knockdown of miR-150-5p rescued the effects of LINC00511 silencing on melanoma cells. Moreover, we identified ADAM19 as a downstream target of miR-150-5p, its overexpression promoted melanoma cell proliferation. Rescue assays confirmed that LINC00511 acted as a competing endogenous RNA, sponging miR-150-5p and increasing ADAM19 expression, culminating in activation of the PI3K/AKT pathway. Conclusion This study establishes LINC00511 as an oncogenic lncRNA in melanoma and defines the novel LINC00511/miR-150-5p/ADAM19 axis, which represents a promising therapeutic target for melanoma treatment. Further investigations targeting this axis hold potential for improving outcomes in melanoma patients.