MicroRNA-381 inhibits cell proliferation and invasion in endometrial carcinoma by targeting the IGF-1R
MicroRNA-381 inhibits cell proliferation and invasion in endometrial carcinoma by targeting the IGF-1R
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MicroRNA-381通过靶向IGF-1R抑制子宫内膜癌细胞增殖和侵袭
DOI：
10.3892/mmr.2017.8288
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发表时间：
2018-03-01
影响因子：
3.4
通讯作者：
Wan, Junhui
中科院分区：
文献类型：
--
作者：
Tu, Chunhua;Wang, Fen;Wan, Junhui
子宫内膜癌（EC）是女性第六常见的恶性肿瘤。 MicroRNA (miRNA) 在人类癌症中作为癌基因或抑癌基因，通过调节多种过程在肿瘤发生和发展中发挥重要作用。因此，进一步研究参与 EC 形成和进展的 miRNA 可能有助于为患有这种疾病的患者制定有效的治疗策略。 miRNA-381 (miR-381) 在多种类型的人类癌症中异常表达。然而，人们对 miR-381 在 EC 中的表达模式、生物学作用和潜在机制知之甚少。在本研究中，结果表明miR-381在EC组织和细胞系中下调。 miR-381表达降低与国际妇产科联合会分期、淋巴结转移和子宫肌层浸润相关。 miR-381的异位表达显着抑制EC细胞的增殖和侵袭。通过一系列实验，胰岛素样生长因子受体 1 (IGF-1R) 被确定为 miR-381 在 EC 中的新直接靶标。此外，IGF-1R在EC组织中高表达，并且与miR-381水平呈负相关。 IGF-1R 过表达部分消除了 miR-381 对 EC 细胞增殖和侵袭的肿瘤抑制作用。 miR-381 靶向 IGF-1R，使 EC 中蛋白激酶 B (AKT) 和细胞外信号调节激酶 (ERK) 信号通路失活。这些结果表明miR-381通过直接靶向IGF-1R并间接调节AKT和ERK信号通路作为EC中的肿瘤抑制因子。因此，miR-381应该作为EC患者的预后生物标志物和新的治疗靶点进行研究。
Endometrial carcinoma (EC) is the sixth most common type of malignant tumor occurring in females. MicroRNAs (miRNAs) serve as oncogenes or tumor suppressors in human cancer and play important roles in tumorigenesis, and tumor development by regulating various processes. Thus, further investigation into miRNAs involved in EC formation and progression may aid in developing effective therapeutic strategies for patients with this disease. miRNA-381 (miR-381) is aberrantly expressed in multiple types of human cancer. However, the expression pattern, biological roles and underlying mechanisms of miR-381 in EC are poorly understood. In the present study, the results showed that miR-381 was downregulated in EC tissues and cell lines. Decreased miR-381 expression correlated with the International Federation of Gynecology and Obstetrics stage, lymph nodes metastasis and myometrial invasion of EC. The ectopic expression of miR-381 significantly inhibited the proliferation and invasion of EC cells. Through a series of experiments, the insulin-like growth factor receptor 1 (IGF-1R) was identified as a novel direct target of miR-381 in EC. Furthermore, IGF-1R was highly expressed in EC tissues and inversely correlated with miR-381 levels. IGF-1R overexpression partially abrogated the tumor-suppressive effects of miR-381 on the proliferation and invasion of EC cells. miR-381 targeted IGF-1R to inactivate the protein kinase B (AKT) and extracellular signal-regulated kinase (ERK) signaling pathways in EC. These results suggest that miR-381 acts as a tumor suppressor in EC by directly targeting IGF-1R, and indirectly regulating the AKT and ERK signaling pathways. Thus, miR-381 should be investigated as a prognostic biomarker and novel therapeutic target for the treatment of patients with EC.