Department of Gastrointestinal surgery, The Third XiangYa Hospital of Central South University, Changsha, Hunan, 410013, China.
Class 25 grade 2016, The Five-Year Program in Clinical Medicine, School of Medicine, University of South China, Hengyang, Hunan, 421001, China.
Cell Death Dis. 2020 Oct 23;11(10):908. doi: 10.1038/s41419-020-03095-4.
The long noncoding RNA (lncRNA) LUCAT1 was recently reported to be upregulated and to play an essential role in multiple cancer types, especially colorectal cancer (CRC), but the molecular mechanisms of LUCAT1 in CRC are mostly unreported. Here, a systematic analysis of LUACT1 expression is performed with data from TCGA database and clinic CRC samples. LUCAT1 is identified as a putative oncogene, which is significantly upregulated in CRC and is associated with poor prognosis. Loss of LUCAT1 restricts CRC proliferative capacities in vitro and in vivo. Mechanically, NCL is identified as the protein binding partner of LUCAT1 by using chromatin isolation by RNA purification coupled with mass spectrometry (ChIRP-MS) and RNA immunoprecipitation assays. We also show that NCL directly binds to LUCAT1 via its putative G-quadruplex-forming regions from nucleotides 717 to 746. The interaction between LUCAT1 and NCL interferes NCL-mediated inhibition of MYC and promote the expression of MYC. Cells lacking LUCAT1 show a decreased MYC expression, and NCL knockdown rescue LUCAT1 depletion-induced inhibition of CRC cell proliferation and MYC expression. Our results suggest that LUCAT1 plays a critical role in CRC cell proliferation by inhibiting the function of NCL via its G-quadruplex structure and may serve as a new prognostic biomarker and effective therapeutic target for CRC.
长链非编码 RNA (lncRNA) LUCAT1 最近被报道上调，并在多种癌症类型中发挥重要作用，特别是结直肠癌 (CRC)，但 LUCAT1 在 CRC 中的分子机制大多尚未报道。在这里，我们使用 TCGA 数据库和临床 CRC 样本中的数据对 LUCAT1 的表达进行了系统分析。LUCAT1 被鉴定为一种推定的癌基因，在 CRC 中显著上调，并与预后不良相关。LUCAT1 的缺失限制了 CRC 在体外和体内的增殖能力。通过使用 RNA 纯化偶联的染色质分离与质谱 (ChIRP-MS) 和 RNA 免疫沉淀测定，我们发现 NCL 是 LUCAT1 的蛋白结合伴侣。我们还表明，NCL 通过其从核苷酸 717 到 746 的假定 G-四联体形成区域直接与 LUCAT1 结合。LUCAT1 和 NCL 之间的相互作用干扰了 NCL 介导的对 MYC 的抑制，并促进了 MYC 的表达。缺乏 LUCAT1 的细胞显示出 MYC 表达降低，而 NCL 敲低可挽救 LUCAT1 耗竭诱导的 CRC 细胞增殖和 MYC 表达抑制。我们的研究结果表明，LUCAT1 通过其 G-四联体结构抑制 NCL 的功能，在 CRC 细胞增殖中发挥关键作用，并且可以作为 CRC 的新的预后生物标志物和有效的治疗靶点。
