Department of Tumor Biological Treatment, The Third Affiliated Hospital of Soochow University, Jiangsu Engineering Research Center for Tumor Immunotherapy, Institute of Cell Therapy, Soochow University, Changzhou, Jiangsu, P. R. China.
Department of Burn and Plastic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P. R. China.
Skin Res Technol. 2024 Sep;30(9):e13910. doi: 10.1111/srt.13910.
The malignancy of melanoma is attributed to its pronounced invasiveness, extensive vascularization, and rapid tumor cell growth and metastasis. LncRNA SLNCR1 is closely associated with a variety of aggressive tumors. However, our understanding of SLNCR1 influences on malignant melanoma growth metastasis mechanism especially proangiogenic mechanism remains unclear.
The expression of SLNCR1 was evaluated in melanoma tissues, adjacent tissues, melanoma cell lines. The abilities of SLNCR1 on proliferation, migration, and angiogenesis of HUVECs were detected by CCK-8, flow cytometry, and Western blot assays. The association between SLNCR1, DNMT1, and SPRY2 was assessed by ChIP, RIP, and Western blot assays. The effect of SLNCR1 on tumor growth was determined using a xenograft model in nude mice.
SLNCR1 was confirmed to be highly expressed in melanoma tissues and cells. CM from melanoma cells transfected with sh-SLNCR1 attenuated proliferation, migration, and angiogenesis of HUVECs. Moreover, loss of SLNCR1 hindered tumor growth and metastasis, as evidenced by reduced tumor size and weight, as well as angiogenesis. Mechanistic studies revealed that SLNCR1 silenced SPRY2 expression, likely through enhancing DNMT1-mediated DNA methylation of SPRY2 promoter.
SLNCR1 is an oncogene that interacts with DNMT1 to mediate SPRY2 methylation, thereby suppressing SPRY2 expression and promoting the angiogenesis and tumor growth in melanoma. SLNCR1 may serve as a potential target for melanoma treatment.
黑色素瘤的恶性程度归因于其显著的侵袭性、广泛的血管生成以及肿瘤细胞的快速生长和转移。LncRNA SLNCR1 与多种侵袭性肿瘤密切相关。然而，我们对 SLNCR1 影响恶性黑色素瘤生长转移机制，尤其是促血管生成机制的理解尚不清楚。
评估黑色素瘤组织、相邻组织、黑色素瘤细胞系中 SLNCR1 的表达。通过 CCK-8、流式细胞术和 Western blot 检测 SLNCR1 对 HUVECs 增殖、迁移和血管生成的能力。通过 ChIP、RIP 和 Western blot 检测 SLNCR1、DNMT1 和 SPRY2 之间的关联。通过裸鼠异种移植模型确定 SLNCR1 对肿瘤生长的影响。
证实 SLNCR1 在黑色素瘤组织和细胞中高表达。转染 sh-SLNCR1 的黑色素瘤细胞 CM 减弱了 HUVECs 的增殖、迁移和血管生成。此外，SLNCR1 的缺失抑制了肿瘤的生长和转移，表现为肿瘤体积和重量的减小以及血管生成的减少。机制研究表明，SLNCR1 沉默 SPRY2 的表达，可能是通过增强 DNMT1 介导的 SPRY2 启动子的 DNA 甲基化。
SLNCR1 是一种癌基因，它与 DNMT1 相互作用，介导 SPRY2 甲基化，从而抑制 SPRY2 的表达，促进黑色素瘤中的血管生成和肿瘤生长。SLNCR1 可能成为黑色素瘤治疗的潜在靶点。
