长链非编码 RNA AFAP1-AS1 通过靶向 miR-653-5p/RAI14 轴促进黑色素瘤的进展。
Long non-coding RNA AFAP1-AS1 accelerates the progression of melanoma by targeting miR-653-5p/RAI14 axis.
机构信息
Department of Bone and Soft Tissue Tumor Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, No.44 Xiaoheyan Road, Dadong District, Shenyang, 110000, Liaoning, China.
Department of Dermatology, the Seventh People's Hospital of Shenyang, Shenyang, 110000, Liaoning Province, China.
出版信息
BMC Cancer. 2020 Mar 30;20(1):258. doi: 10.1186/s12885-020-6665-2.
BACKGROUND
Melanoma is the most aggressive skin cancer that derived from pigment cells, accounting for the majority of the skin-cancer-related deaths. Despite great development and evolution have been made in surgery, radiotherapy and adjuvant chemotherapy, the prognosis of melanoma patients exhibited no significant improvement. Long noncoding RNAs (lncRNAs) are frequently dysregulated and involved in the development of cancers. LncRNA AFAP1-AS1 has been explored in various cancers, whereas its role and regulatory mechanism in melanoma are not well understood.
METHODS
The expression of AFAP1-AS1 was detected by qRT-PCR. CCK-8, colony formation, transwell and western blot assays were performed to investigate the biological role of AFAP1-AS1 in melanoma. Male BALB/c nude mice were applied for in vivo experiments. The interaction among AFAP1-AS1, miR-653-5p and RAI14 was investigated by RNA pull down, RIP and luciferase reporter assays.
RESULTS
AFAP1-AS1 was highly expressed in melanoma cell lines. Suppression of AFAP1-AS1 impaired cell proliferation, migration, invasion and EMT in melanoma. Moreover, AFAP1-AS1 was a ceRNA of RAI14 by competitively binding with miR-653-5p. Besides, miR-653-5p overexpression or RAI14 inhibition could repress tumor growth. Eventually, rescue assays indicated that the function of AFAP1-AS1 in the cellular process of melanoma was dependent on miR-653-5p and RAI14.
CONCLUSIONS
AFAP1-AS1 exerts its oncogenic function in melanoma by targeting miR-653-5p/RAI14 axis.
背景
黑色素瘤是最具侵袭性的皮肤癌，起源于色素细胞，占皮肤癌相关死亡人数的大多数。尽管在手术、放疗和辅助化疗方面取得了巨大的发展和进步，但黑色素瘤患者的预后并未得到显著改善。长链非编码 RNA（lncRNA）经常失调，并参与癌症的发展。LncRNA AFAP1-AS1 已在多种癌症中得到研究，但其在黑色素瘤中的作用和调控机制尚不清楚。
方法
通过 qRT-PCR 检测 AFAP1-AS1 的表达。通过 CCK-8、集落形成、Transwell 和 Western blot 实验研究 AFAP1-AS1 在黑色素瘤中的生物学作用。雄性 BALB/c 裸鼠用于体内实验。通过 RNA 下拉、RIP 和荧光素酶报告基因实验研究 AFAP1-AS1、miR-653-5p 和 RAI14 之间的相互作用。
结果
AFAP1-AS1 在黑色素瘤细胞系中高表达。抑制 AFAP1-AS1 可抑制黑色素瘤细胞的增殖、迁移、侵袭和 EMT。此外，AFAP1-AS1 通过与 miR-653-5p 竞争结合作为 RAI14 的 ceRNA。此外，miR-653-5p 过表达或 RAI14 抑制可抑制肿瘤生长。最终，挽救实验表明，AFAP1-AS1 在黑色素瘤细胞过程中的功能依赖于 miR-653-5p 和 RAI14。
结论
AFAP1-AS1 通过靶向 miR-653-5p/RAI14 轴在黑色素瘤中发挥致癌作用。
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