ABSTRACT

Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. Long non-coding RNAs (lncRNAs) have been increasingly reported to serve vital parts in malignancies including CRC. Although cancer susceptibility 21 (CASC21) has been uncovered to play a part in CRC, its mechanism still needs further explanation. Thus, our study aimed to further explore the influence and mechanism of CASC21 in CRC progression. Quantitative real-time RT-PCR and western blot were performed to detect gene expression; a series of functional assays were performed to investigate the effect of CASC21 on CRC cells; in vivo tumour growth was evaluated via the nude mice xenograft model. The results revealed that CASC21 facilitated CRC cell proliferation, migration, epithelial-mesenchymal transition (EMT) and stemness. In addition, CASC21 was co-expressed with and bound to transcription factor POU5F1B (POU class 5 homeobox 1B). CASC21 recruited POU5F1B to HGH1 promoter to activate the transcription of HGH1 homolog. Also, CASC21 served as a competitive endogenous RNA (ceRNA) to up-regulate HGH1 via endogenously sponging miR-485-5p. Moreover, HGH1 overexpression counteracted the suppression of CASC21 deficiency on CRC tumour growth. In summary, our study indicated that CASC21 enhanced the expression of HGH1 to promote the malignancy of CRC by recruiting POU5F1B and sponging miR-485-5p, suggesting a key role of CASC21 in CRC progression.

摘要

结直肠癌 (CRC) 是全球癌症相关死亡的主要原因之一。越来越多的报道称，长链非编码 RNA (lncRNA) 在包括 CRC 在内的恶性肿瘤中发挥重要作用。尽管癌症易感性 21 (CASC21) 在 CRC 中起作用，但其机制仍需进一步解释。因此，我们的研究旨在进一步探讨 CA​​SC21 在 CRC 进展中的影响和机制。进行定量实时RT-PCR和蛋白质印迹以检测基因表达；进行了一系列功能测定以研究 CASC21 对 CRC 细胞的影响；体内通过裸鼠异种移植模型评估肿瘤生长。结果表明，CASC21促进了CRC细胞增殖、迁移、上皮-间质转化（EMT）和干细胞性。此外，CASC21 与转录因子 POU5F1B（POU 5 类同源框 1B）共表达并结合。CASC21 将 POU5F1B 募集到 HGH1 启动子以激活 HGH1 同源物的转录。此外，CASC21 作为竞争性内源性 RNA (ceRNA) 通过内源性海绵状 miR-485-5p 上调 HGH1。此外，HGH1 过表达抵消了 CASC21 缺乏对 CRC 肿瘤生长的抑制。总之，我们的研究表明 CASC21 通过招募 POU5F1B 和海绵状 miR-485-5p 增强 HGH1 的表达以促进 CRC 的恶性，这表明 CASC21 在 CRC 进展中的关键作用。