Ophthalmology of Xi'an First Hospital, Xi'an, Shaanxi 710002, China.
Ophthalmology of Xi'an First Hospital, Xi'an, Shaanxi 710002, China.
Eur J Pharmacol. 2019 Jan 15;843:210-216. doi: 10.1016/j.ejphar.2018.11.028. Epub 2018 Nov 22.
Accumulating evidence demonstrated that abnormal expression of long non-coding RNAs (lncRNAs) was closely associated with cancer development including retinoblastoma (RB). LncRNA X inactive specific transcript (XIST) has been found to function as an oncogene or a tumor suppressor in several cancers. However, the role and underlying mechanism of XIST in RB have not been clarified. The expression of XIST, microRNA (miR)- 101, zinc finger E-box binding homeobox (ZEB) 1, and ZEB2 was detected in human RB tissues and cell lines. The effects of XIST on the proliferation, migration, invasion, epithelial to mesenchymal transition (EMT), and apoptosis of RB cells were evaluated after downregulation of XIST. Furthermore, the mechanism of XIST was mainly focused on miR-101/ZEB1 or ZEB2 signaling. We found the expression of XIST, ZEB1 and ZEB2 was increased, whereas miR-101 was reduced in RB tissues and cells. Knockdown of XIST significantly suppressed the proliferation, migration, invasion and EMT, but promoted the apoptosis and caspase-3 activity. Moreover, we found that XIST functioned as a competing endogenous RNA (ceRNA) for miR-101 to regulate the de-repression of its endogenous targets ZEB1 and ZEB2. In conclusion, these findings suggest that XIST may facilitate the progression of RB through acting as a ceRNA for miR-101 to mediate the expression of ZEB1 and ZEB2. This may provide novel therapeutic options for RB.
越来越多的证据表明，长链非编码 RNA（lncRNA）的异常表达与癌症的发生密切相关，包括视网膜母细胞瘤（RB）。已经发现 X 染色体失活特异性转录物（XIST）lncRNA 在几种癌症中作为癌基因或肿瘤抑制因子发挥作用。然而，XIST 在 RB 中的作用及其潜在机制尚未阐明。检测了 XIST、微小 RNA（miR）-101、锌指 E 盒结合同源盒（ZEB）1 和 ZEB2 在人 RB 组织和细胞系中的表达。下调 XIST 后，评估 XIST 对 RB 细胞增殖、迁移、侵袭、上皮间质转化（EMT）和凋亡的影响。此外，主要关注 XIST 对 miR-101/ZEB1 或 ZEB2 信号的作用机制。我们发现 XIST、ZEB1 和 ZEB2 的表达在 RB 组织和细胞中增加，而 miR-101 减少。XIST 敲低显著抑制增殖、迁移、侵袭和 EMT，但促进凋亡和 caspase-3 活性。此外，我们发现 XIST 作为 miR-101 的竞争性内源性 RNA（ceRNA）发挥作用，以调节其内源性靶标 ZEB1 和 ZEB2 的去抑制。总之，这些发现表明，XIST 可能通过作为 miR-101 的 ceRNA 来调节 ZEB1 和 ZEB2 的表达，从而促进 RB 的进展。这可能为 RB 提供新的治疗选择。
