Clinical College of TCM, Hubei University of Chinese Medicine, Wuhan, 410063 Hubei Province, China.
Dermatology, Yancheng TCM Hospital Affiliated to Nanjing University of Chinese Medicine, Yancheng, 224000 Jiangsu Province, China.
Biomed Res Int. 2022 Jun 30;2022:3546795. doi: 10.1155/2022/3546795. eCollection 2022.
Melanoma has become the most severe sort of skin cancer, deriving from the pigment-producing melanocytes. Existing research has validated that long noncoding RNAs (lncRNAs) have critical function in the progression of cancers. LINC00518 has been studied in cutaneous melanoma; however, the molecular mechanism of LINC00518 in melanoma needs in-depth investigation. In our study, LINC00518 was revealed to be upregulated in melanoma tissues and cells, and melanoma patients in high LINC00518 expression group had poorer prognosis as depicted in GEPIA database. Functional assays revealed that LINC00518 depletion inhibited cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, MITF was confirmed to be upregulated in melanoma tissues and cells, and melanoma patients in high MITF expression group had poorer prognosis as displayed in GEPIA database. MITF expression was positively connected to LINC00518 expression. Additionally, results of mechanism assays uncovered EIF4A3 could bind with LINC00518 and MITF, and LINC00518 recruited EIF4A3 to stabilize MITF mRNA. Finally, it was demonstrated that upregulation of MITF could partially abrogate the inhibitory impact of LINC00518 knockdown on melanoma cell malignant behaviors. To summarize, LINC00518 promotes the malignant processes of melanoma cells through targeting EIF4A3/MITF axis, which might provide novel potential biomarkers for melanoma prognosis.
黑色素瘤已成为最严重的皮肤癌，源于产生色素的黑素细胞。现有研究已经证实，长链非编码 RNA（lncRNA）在癌症的进展中具有关键作用。LINC00518 已在皮肤黑色素瘤中进行了研究；然而，LINC00518 在黑色素瘤中的分子机制仍需要深入研究。在我们的研究中，LINC00518 在黑色素瘤组织和细胞中被上调，并且 GEPIA 数据库显示高表达 LINC00518 的黑色素瘤患者预后较差。功能测定表明，LINC00518 的缺失抑制了细胞增殖、迁移、侵袭和上皮-间充质转化（EMT）。此外，MITF 在黑色素瘤组织和细胞中被上调，并且 GEPIA 数据库显示高表达 MITF 的黑色素瘤患者预后较差。MITF 的表达与 LINC00518 的表达呈正相关。此外，机制测定结果表明，EIF4A3 可以与 LINC00518 和 MITF 结合，并且 LINC00518 招募 EIF4A3 来稳定 MITF mRNA。最后，结果表明上调 MITF 可以部分抵消 LINC00518 敲低对黑色素瘤细胞恶性行为的抑制作用。总之，LINC00518 通过靶向 EIF4A3/MITF 轴促进黑色素瘤细胞的恶性进程，这可能为黑色素瘤的预后提供新的潜在生物标志物。
