Wang Qin, Zhu Weipei
Department of Gynaecology and Obstetrics, The First People's Hospital of Kunshan, Kunshan, Jiangsu 215000, P.R. China.
Department of Gynaecology and Obstetrics, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215004, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1291-1298. doi: 10.3892/etm.2019.7713. Epub 2019 Jun 26.
An accumulation of evidence has demonstrated that abnormal microRNA (miRNA or miR) expression is associated with different types of cancer, including endometrial cancer (EC). The dysregulation of miRNAs may serve important roles in the development and progression of EC by regulating multiple aggressive biological behaviors, including cell proliferation, apoptosis, metastasis and angiogenesis. An in-depth understanding of the miRNAs associated with EC initiation and progression may be crucial for identifying successful therapeutic techniques. miR-873 has been demonstrated to be dysregulated in different types of cancer. However, the expression status and regulatory roles of miR-873 are yet to be elucidated in EC. In the present study, reverse transcription-quantitative PCR was carried out to detect miR-873 expression in EC tissues and cell lines. Cell Counting Kit-8 and invasion assays were utilized to determine the influence of miR-873 on the proliferation and invasion of EC cells. miR-873 expression was revealed to be downregulated in EC tissues and cell lines. Decreased miR-873 expression was significantly associated with International Federation of Gynecology and Obstetrics stage and lymph node metastasis of patients with EC. Functional assays revealed that resumed miR-873 expression suppressed the proliferation and invasion of EC cells. Additionally, hepatoma-derived growth factor (HDGF) was indicated to be a direct target gene of miR-873 in EC cells. HDGF was highly expressed in EC tissues and inversely correlated with miR-873 expression. HDGF silencing also imitated the tumor-suppressor activity of miR-873 overexpression in EC cells. A series of rescue experiments identified that recovered HDGF expression hindered the anti-proliferative and anti-invasive roles of miR-873 upregulation in EC cells. In conclusion, the present study indicated that miR-873 serves an important role as a tumor suppressor in EC development by directly targeting HDGF. The results may provide a novel insight into clinical treatments, which can be used to prevent EC aggression.
大量证据表明，异常的微小RNA（miRNA或miR）表达与包括子宫内膜癌（EC）在内的不同类型癌症相关。miRNA的失调可能通过调节多种侵袭性生物学行为，包括细胞增殖、凋亡、转移和血管生成，在EC的发生和发展中发挥重要作用。深入了解与EC起始和进展相关的miRNA对于确定成功的治疗技术可能至关重要。已证明miR-873在不同类型癌症中表达失调。然而，miR-873在EC中的表达状态和调控作用尚待阐明。在本研究中，进行了逆转录定量PCR以检测EC组织和细胞系中miR-873的表达。利用细胞计数试剂盒-8和侵袭试验来确定miR-873对EC细胞增殖和侵袭的影响。结果显示，EC组织和细胞系中miR-873表达下调。miR-873表达降低与EC患者的国际妇产科联盟分期和淋巴结转移显著相关。功能试验表明，恢复miR-873表达可抑制EC细胞的增殖和侵袭。此外，肝癌衍生生长因子（HDGF）被表明是EC细胞中miR-873的直接靶基因。HDGF在EC组织中高表达，且与miR-873表达呈负相关。HDGF沉默也模拟了miR-873过表达在EC细胞中的肿瘤抑制活性。一系列挽救实验表明，恢复HDGF表达会阻碍miR-873上调对EC细胞的抗增殖和抗侵袭作用。总之，本研究表明miR-873通过直接靶向HDGF在EC发展中作为肿瘤抑制因子发挥重要作用。这些结果可能为临床治疗提供新的见解，可用于预防EC侵袭。
