He Saifei, Wang Guangdong, Ni Jing, Zhuang Juhua, Zhuang Suiliang, Wang Guoyu, Ye Ying, Xia Wei
Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China.
Department of Research and Development, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China.
Oncol Res. 2018 Oct 17;26(9):1355-1363. doi: 10.3727/096504018X15154094331876. Epub 2018 Jan 10.
Dysregulated microRNA (miRNA) expression is involved in the occurrence and development of colorectal cancer (CRC) through the regulation of various important physiological events. Hence, miRNAs may be used as effective targets for CRC treatment; however, this hypothesis warrants further investigation. miRNA-511 (miR-511) plays vital roles in the progression of different tumor types. However, the expression, exact role, and the mechanisms underlying the regulation of colorectal carcinogenesis and progression by miR-511 remain poorly understood. This study presents that miR-511 expression was decreased in CRC tissues and cell lines compared with that in adjacent nonneoplastic tissues and normal human colon epithelium cell lines, respectively. The enforced expression of miR-511 in CRC cells significantly reduced cell proliferation and invasion. Hepatoma-derived growth factor (HDGF) was mechanically validated as a direct target of miR-511 in CRC. Furthermore, miR-511 was negatively associated with HDGF in CRC tissues. The restored HDGF expression can abrogate the tumor-suppressive roles of miR-511 in CRC cells. More importantly, miR-511 overexpression suppressed the PI3K/AKT signaling pathway in CRC. These results suggest that miR-511 can potentially serve as a therapeutic target for the therapy of patients with CRC.
失调的微小RNA（miRNA）表达通过调控各种重要的生理事件参与结直肠癌（CRC）的发生和发展。因此，miRNA可能作为CRC治疗的有效靶点；然而，这一假说有待进一步研究。miRNA-511（miR-511）在不同肿瘤类型的进展中发挥着重要作用。然而，miR-511在结直肠癌发生和进展中的表达、确切作用及调控机制仍知之甚少。本研究表明，与相邻非肿瘤组织和正常人类结肠上皮细胞系相比，miR-511在CRC组织和细胞系中的表达分别降低。在CRC细胞中强制表达miR-511可显著降低细胞增殖和侵袭。肝癌衍生生长因子（HDGF）在CRC中被机械验证为miR-511的直接靶点。此外，在CRC组织中，miR-511与HDGF呈负相关。恢复HDGF表达可消除miR-511在CRC细胞中的肿瘤抑制作用。更重要的是，miR-511过表达抑制了CRC中的PI3K/AKT信号通路。这些结果表明，miR-511有可能作为CRC患者治疗的靶点。
