Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China; Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Nanjing, 210042, China.
Department of Pathology, Institute of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, China.
Biomed Pharmacother. 2017 Dec;96:1371-1379. doi: 10.1016/j.biopha.2017.11.060. Epub 2017 Nov 28.
Accumulating evidences have suggested that focally amplified lncRNA on chromosome 1 (FALEC) serves as an oncogenic long non-coding RNA (lncRNA) and has been identified to be dysregulated in various tumors. However, the expression, clinical values, and biological function of FALEC in melanoma are still unknown. In this study we detected the expression level of FALEC in tumor tissues and cell lines and measured the prognostic value of FALEC for melanoma patients and the biological effects of FALEC on melanoma cell proliferation, cell cycle, and apoptosis. Our results indicated that FALEC was more highly expressed in melanoma tissues and cell lines than in non-neoplastic nevi tissues and normal cell lines. Moreover, functional assays showed that silenced FALEC suppressed the proliferation of melanoma cells, resulted in cell cycle arrest, and induced apoptosis. Mechanically, we discovered that FALEC boosted melanoma progression via epigenetically repressing p21 through recruiting EZH2 to the promoter of p21. Generally, our results suggested that FALEC acted as an oncogene in melanoma and had the potential to be a prognostic biomarker and therapeutic target for melanoma.
越来越多的证据表明，染色体 1 上的局灶性扩增长非编码 RNA（FALEC）作为一种致癌的长非编码 RNA（lncRNA），已被确定在各种肿瘤中失调。然而，FALEC 在黑色素瘤中的表达、临床价值和生物学功能仍不清楚。在这项研究中，我们检测了 FALEC 在肿瘤组织和细胞系中的表达水平，并测量了 FALEC 对黑色素瘤患者的预后价值以及 FALEC 对黑色素瘤细胞增殖、细胞周期和细胞凋亡的生物学影响。我们的结果表明，FALEC 在黑色素瘤组织和细胞系中的表达水平高于非肿瘤性痣组织和正常细胞系。此外，功能分析表明，沉默 FALEC 抑制了黑色素瘤细胞的增殖，导致细胞周期停滞，并诱导细胞凋亡。从机制上讲，我们发现 FALEC 通过募集 EZH2 到 p21 的启动子来抑制 p21 的表观遗传，从而促进黑色素瘤的进展。总的来说，我们的研究结果表明，FALEC 在黑色素瘤中作为癌基因发挥作用，有可能成为黑色素瘤的预后生物标志物和治疗靶点。
