Department of General Surgery, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China.
Clin Exp Pharmacol Physiol. 2020 Apr;47(4):703-712. doi: 10.1111/1440-1681.13230. Epub 2020 Jan 9.
Long non-coding RNAs (lncRNAs) have recently emerged as key regulators of the occurrence and progression of various human cancers, including colorectal cancer. However, the regulatory mechanism of lncRNAs in the tumorigenesis of colorectal cancer remains poorly understood. In this study, we aimed to elucidate the potential role of lncRNA HCG18 in colorectal cancer. Herein, we found that HCG18 expression was significantly upregulated in colorectal cancer tissues and cell lines. Knockdown of HCG18 significantly inhibited the growth and invasion of colorectal cancer cells, while its overexpression had the opposite effect. Moreover, HCG18 was identified as a sponge of miR-1271. Our results showed that knockdown of HCG18 markedly upregulated miR-1271 expression in colorectal cancer cells. Notably, HCG18 expression was inversely correlated with miR-1271 expression in colorectal cancer specimens. Further investigation revealed that HCG18 contributed to the enhancement of MTDH/Wnt/β-catenin signalling in colorectal cancer cells. The antitumour effect of HCG18 inhibition was significantly reversed by miR-1271 inhibition or MTDH overexpression. Overall, the results of our study demonstrate that HCG18 exerts a potential oncogenic function in colorectal cancer by enhancing MTDH/Wnt/β-catenin signalling via sponging of miR-1271, highlighting the importance of HCG18/miR-1271/ MTDH/Wnt/β-catenin signalling in the progression of colorectal cancer.
长链非编码 RNA（lncRNA）最近被发现是多种人类癌症（包括结直肠癌）发生和发展的关键调节因子。然而，lncRNA 在结直肠癌发生中的调控机制仍知之甚少。在本研究中，我们旨在阐明 lncRNA HCG18 在结直肠癌中的潜在作用。在此，我们发现 HCG18 在结直肠癌组织和细胞系中表达明显上调。HCG18 敲低显著抑制结直肠癌细胞的生长和侵袭，而其过表达则产生相反的效果。此外，HCG18 被鉴定为 miR-1271 的海绵体。我们的结果表明，HCG18 敲低可显著上调结直肠癌细胞中的 miR-1271 表达。值得注意的是，HCG18 在结直肠癌标本中的表达与 miR-1271 的表达呈负相关。进一步的研究表明，HCG18 通过海绵吸附 miR-1271 促进 MTDH/Wnt/β-catenin 信号通路在结直肠癌细胞中的增强。抑制 HCG18 可显著逆转 miR-1271 抑制或 MTDH 过表达对其抗肿瘤作用的逆转。综上所述，我们的研究结果表明，HCG18 通过海绵吸附 miR-1271 增强 MTDH/Wnt/β-catenin 信号通路，从而在结直肠癌中发挥潜在的致癌功能，强调了 HCG18/miR-1271/MTDH/Wnt/β-catenin 信号通路在结直肠癌进展中的重要性。
