Department of Gastrointestinal Surgery, Second Clinical Medical College of Jinan University, Shenzhen People's Hospital, Shenzhen, China.
Shenzhen Ritzcon Biological Technology Co, Ltd, Shenzhen, Guangdong, China.
J Cell Biochem. 2019 Apr;120(4):6071-6077. doi: 10.1002/jcb.27893. Epub 2018 Oct 25.
Long noncoding RNAs (lncRNA) have been demonstrated to extensively participate in a wide spectrum of biological activities ranging from embryogenesis and cancer progression. HOX transcript antisense RNA (Hotair), an lncRNA located in the HOXC locus, has been reported to play an important role in carcinogenesis. As a well-known oncogene, it potentiates cancer metastasis and tumor progression. And it also serves as a biomarker for poor prognosis and tumor recurrence. In this study, Hotair was found to be upregulated in colorectal cancer (CRC) cells and clinical specimens. Further investigation showed that knockdown of Hotair dramatically suppressed cell proliferation and colony formation, suggesting that Hotair may stimulate tumorigenesis of CRC. The enhancer of zeste homolog 2 (EZH2), a regulator of epigenetic modification, was upregulated in CRC cells and clinical samples. And the silence of EZH2 significantly suppressed cell viability and colony formation. Furthermore, the RNA immunoprecipitation assay revealed that Hotair directly bound EZH2 in CRC cells. In conclusion, Hotair mediated tumorigenesis via recruiting EZH2, which might shed light on the development of a novel therapeutic approach for patients with CRC.
长链非编码 RNA（lncRNA）已被证明广泛参与从胚胎发生和癌症进展等多种生物活性。位于 HOXC 基因座的 lncRNA HOX 转录反义 RNA（Hotair）已被报道在致癌作用中发挥重要作用。作为一个众所周知的癌基因，它增强了癌症转移和肿瘤进展。并且，它还可用作预后不良和肿瘤复发的生物标志物。在这项研究中，发现 Hotair 在结直肠癌（CRC）细胞和临床标本中上调。进一步的研究表明，Hotair 的敲低显著抑制了细胞增殖和集落形成，表明 Hotair 可能刺激 CRC 的肿瘤发生。增强子的外显子 2（EZH2）是表观遗传修饰的调节剂，在 CRC 细胞和临床样本中上调。EZH2 的沉默显著抑制了细胞活力和集落形成。此外，RNA 免疫沉淀测定显示 Hotair 在 CRC 细胞中直接结合 EZH2。总之，Hotair 通过招募 EZH2 介导肿瘤发生，这可能为 CRC 患者开发新的治疗方法提供了启示。
