Department of General Surgery, Xinhua Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
J Biol Regul Homeost Agents. 2020 Jan-Feb;34(1):49-56. doi: 10.23812/19-526-A-FULL_ARTICLE.
Dysregulation of lncRNA cancer susceptibility candidate 2 (CASC2) is involved in the pathogenesis of multiple malignancies. However, the underlying mechanisms by which lncRNA CASC2 regulates the proliferation of hemangiomas (HAs) remain undocumented. Herein, the expression levels of lncRNA CASC2 and VEGF in proliferating or involuting phase HAs were assessed by qRT-PCR analysis, and the effects of lncRNA CASC2 on HAs cell growth were evaluated by MTT, colony formation assays and Western blot analysis. lncRNA CASC2 specific binding with miR-18a-5p was confirmed by luciferase report assay. Consequently, we found that the expression of lncRNA CASC2 was reduced in proliferating phase HAs as compared with the involuting phase HAs or normal tissues, and possessed a negative correlation with VEGF expression in proliferating phase HAs. Restored expression of lncRNA CASC2 repressed cell viability and colony formation and downregulated VEGF expression, while silencing lncRNA CASC2 showed the opposite effects. Moreover, lncRNA CASC2 was confirmed to bind with miR-18a-5p, which could reverse lncRNA CASC2-induced anti-proliferative effects by targeting FBXL3 in HAs cells. Altogether, our findings demonstrated that lncRNA CASC2 suppressed the growth of HAs cells by regulating miR-18a-5p/FBXL3 axis.
长链非编码 RNA 癌症易感性候选物 2（CASC2）的失调参与了多种恶性肿瘤的发病机制。然而，lncRNA CASC2 调节血管瘤（HAs）增殖的潜在机制尚未有文献记载。在此，通过 qRT-PCR 分析评估了增殖期或消退期 HAs 中 lncRNA CASC2 和 VEGF 的表达水平，并通过 MTT、集落形成测定和 Western blot 分析评估了 lncRNA CASC2 对 HAs 细胞生长的影响。通过荧光素酶报告测定证实了 lncRNA CASC2 与 miR-18a-5p 的特异性结合。结果发现，与消退期 HAs 或正常组织相比，增殖期 HAs 中 lncRNA CASC2 的表达降低，并且与增殖期 HAs 中的 VEGF 表达呈负相关。恢复表达 lncRNA CASC2 抑制细胞活力和集落形成，并下调 VEGF 表达，而沉默 lncRNA CASC2 则表现出相反的效果。此外，lncRNA CASC2 被证实与 miR-18a-5p 结合，后者可以通过靶向 FBXL3 逆转 HAs 细胞中 lncRNA CASC2 诱导的抗增殖作用。总之，我们的研究结果表明，lncRNA CASC2 通过调节 miR-18a-5p/FBXL3 轴抑制 HAs 细胞的生长。
