Department of Gastrointestinal Tumor Surgery, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, Henan, China.
Department of Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China.
J Cell Physiol. 2019 May;234(5):7247-7256. doi: 10.1002/jcp.27482. Epub 2018 Oct 28.
Colorectal cancer (CRC) is one of the leading causes of cancer-related death worldwide. Currently, an increasing evidence showed that circular RNAs (circRNAs) play important roles in tumor progression. However, the effects and underlying mechanisms of circRNAs in CRC progression remain unclear. In the present study, through circRNA high-throughput sequencing and quantitative real-time polymerase chain reaction, we identified that hsa_circ_0136666 was significantly overexpressed in CRC tissues and cell lines. High hsa_circ_0136666 expression was associated with poor overall survival of patients with CRC. In vitro function assays showed that hsa_circ_0136666 inhibition suppressed CRC cell proliferation, migration, invasion, and arrested CRC cells in the G0/G1 phase. Furthermore, we showed that hsa_circ_0136666 inhibition reduced CRC cell growth in vivo. Mechanistically, we revealed that hsa_circ_0136666 could increase SH2B1 expression via competitively binding miR-136 in CRC cells. In addition, SH2B1 overexpression could reverse the effects of hsa_circ_0136666 inhibition on CRC cell progression. In conclusion, our data suggested that hsa_circ_0136666 could promote CRC cell progression via the miR-136/SH2B1 axis, elucidating a novel approach to improve the effectiveness of CRC treatment.
结直肠癌(CRC)是全球癌症相关死亡的主要原因之一。目前,越来越多的证据表明环状 RNA(circRNA)在肿瘤进展中发挥重要作用。然而,circRNA 在 CRC 进展中的作用及其潜在机制尚不清楚。在本研究中,我们通过 circRNA 高通量测序和实时定量聚合酶链反应,鉴定出 hsa_circ_0136666 在 CRC 组织和细胞系中显著过表达。高 hsa_circ_0136666 表达与 CRC 患者总体生存不良相关。体外功能实验表明,hsa_circ_0136666 抑制可抑制 CRC 细胞增殖、迁移、侵袭,并使 CRC 细胞停滞在 G0/G1 期。此外,我们还表明 hsa_circ_0136666 抑制可减少 CRC 细胞在体内的生长。机制上,我们揭示 hsa_circ_0136666 可通过竞争性结合 CRC 细胞中的 miR-136 增加 SH2B1 表达。此外,SH2B1 过表达可逆转 hsa_circ_0136666 抑制对 CRC 细胞进展的影响。总之,我们的数据表明 hsa_circ_0136666 可通过 miR-136/SH2B1 轴促进 CRC 细胞进展,为提高 CRC 治疗效果提供了一种新方法。