Department of Urology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China.
Department of Urology, Huai'an Second People's Hospital and The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.
J Cell Biochem. 2019 Apr;120(4):6330-6338. doi: 10.1002/jcb.27920. Epub 2018 Oct 25.
Long noncoding RNAs (lncRNAs) have been reported to take part in intracellular RNA regulatory networks and play important roles in a lot of pathological processes. Currently, lncRNA X-inactive specific transcript (XIST) has been proved to regulate cell migration, proliferation, and apoptosis in a series of cancers. In this study, we explored whether XIST can affect cell proliferation, migration, and apoptosis in bladder cancer. The influences of XIST on the cell proliferation, cell cycle, and apoptosis were detected in bladder cancer cells. The effect of XIST on the migration of bladder cancer cells was examined by cell migration assay. Through RNA immunoprecipitation and chromatin immunoprecipitation assays, the binding relationship between XIST and TET1 and the regulatory mechanism of TET1 on p53 were examined. Western blot was performed to detect p53 after knockdown or overexpression of XIST. We found that knockdown of XIST suppressed cell migration and proliferation in vitro. Mechanistically, we confirmed that lncRNA XIST participates in bladder cancer by downregulating p53 via binding to TET1. In conclusion, our research revealed the potential role of XIST-TET1-p53 regulatory network in bladder cancer.
长链非编码 RNA（lncRNA）已被报道参与细胞内 RNA 调控网络，并在许多病理过程中发挥重要作用。目前，X 失活特异性转录本（XIST）已被证明可调节一系列癌症中的细胞迁移、增殖和凋亡。在本研究中，我们探讨了 XIST 是否可以影响膀胱癌中的细胞增殖、迁移和凋亡。通过检测 XIST 对膀胱癌细胞增殖、细胞周期和凋亡的影响，研究了 XIST 对膀胱癌细胞迁移的影响。通过 RNA 免疫沉淀和染色质免疫沉淀实验，检测了 XIST 与 TET1 的结合关系以及 TET1 对 p53 的调控机制。通过 Western blot 检测 XIST 敲低或过表达后 p53 的表达。我们发现，XIST 敲低抑制了体外细胞的迁移和增殖。从机制上讲，我们通过证实 lncRNA XIST 通过与 TET1 结合来下调 p53，从而参与膀胱癌的发生。总之，我们的研究揭示了 XIST-TET1-p53 调控网络在膀胱癌中的潜在作用。
