Department of Hepatobiliary Surgery, Wenzhou Central Hospital.
Department of Dermatology.
Melanoma Res. 2019 Jun;29(3):254-262. doi: 10.1097/CMR.0000000000000560.
Long noncoding RNA X-inactive specific transcript (XIST) was confirmed to participate in the development of many cancers. However, the function of XIST in malignant melanoma (MM) remained largely unknown. In the current study, we found that the XIST expression level was upregulated in MM tissues and cell lines. In addition, the growth rate of MM cells transfected with silencing XIST was significantly decreased compared with that with silencing normal control. XIST knockdown inhibited proliferation and migration in MM cells and increased the oxaliplatin sensitivity of oxaliplatin-resistant MM cells. Bioinformatics analysis showed that XIST acts as a molecular sponge for miR-21 and miR-21 directly targets with 3'-UTR of PI3KR1. Furthermore, XIST knockdown inhibited PI3KRI and AKT expression, and promoted Bcl-2 and Bax expression. In short, the current study showed that XIST was a crucial regulator in progression and oxaliplatin resistance of MM, providing a novel insight into the pathogenesis and underlying therapeutic target for MM.
长链非编码 RNA X 失活特异性转录本(XIST)被证实参与许多癌症的发生发展。然而,XIST 在恶性黑色素瘤(MM)中的作用在很大程度上仍不清楚。在本研究中,我们发现 XIST 在 MM 组织和细胞系中表达上调。此外,与沉默正常对照相比,沉默 XIST 转染的 MM 细胞的生长速度明显降低。XIST 敲低抑制 MM 细胞的增殖和迁移,并增加奥沙利铂耐药 MM 细胞对奥沙利铂的敏感性。生物信息学分析表明,XIST 作为 miR-21 的分子海绵,miR-21 直接靶向 PI3KR1 的 3'UTR。此外,XIST 敲低抑制 PI3KRI 和 AKT 表达,促进 Bcl-2 和 Bax 表达。总之,本研究表明 XIST 是 MM 进展和奥沙利铂耐药的关键调节因子,为 MM 的发病机制和潜在治疗靶点提供了新的见解。