Department of Radiation Oncology, The First Hospital of Qinhuangdao, Qinhuangdao, China.
Department of Gynecology, The First Hospital of Qinhuangdao, Qinhuangdao, China.
Cancer Sci. 2019 Mar;110(3):913-925. doi: 10.1111/cas.13921. Epub 2019 Jan 19.
Emerging evidence has indicated that microRNAs (miRNAs) play an important role in cervical cancer (CC). However, the role of miRNA (miR)-665 in cervical cancer remains unclear. The aim of the present study was to investigate the potential functions of miR-665 in CC and to identify the underlying mechanisms of action. Herein, we show that miR-665 was downregulated in CC tissues and cell lines, which is negatively correlated with tumor size, distant metastasis, advanced TNM stage and poor prognosis. Functionally, miR-665 inhibited cell proliferation, migration and invasion and resistance of cisplatin for CC cells, as well as tumor growth. We validated that transforming growth factor beta receptor 1 (TGFBR1) was a direct target of miR-665 and mediated the ERK/SMAD pathway. In addition, we identified miR-665 as the competing endogenous RNA for long noncoding (lnc)-DANCR. These observations suggested that lnc-DANCR-mediated miR-665 downregulation regulates the malignant phenotype of CC cells by targeting TGFBR1 through the ERK/SMAD pathway, which may present a pathway for novel therapeutic stratagems for CC therapy.
新出现的证据表明 microRNAs（miRNAs）在宫颈癌（CC）中发挥着重要作用。然而，miRNA（miR）-665 在宫颈癌中的作用仍不清楚。本研究旨在探讨 miR-665 在 CC 中的潜在功能，并确定其作用机制。本研究显示，miR-665 在 CC 组织和细胞系中下调，与肿瘤大小、远处转移、晚期 TNM 分期和预后不良呈负相关。功能上，miR-665 抑制 CC 细胞的增殖、迁移和侵袭以及顺铂耐药性，并抑制肿瘤生长。我们验证了转化生长因子β受体 1（TGFBR1）是 miR-665 的直接靶标，并介导了 ERK/SMAD 通路。此外，我们发现 miR-665 是长链非编码（lnc）-DANCR 的竞争性内源性 RNA。这些观察结果表明，lnc-DANCR 介导的 miR-665 下调通过靶向 TGFBR1 调节 CC 细胞的恶性表型，通过 ERK/SMAD 通路，这可能为 CC 治疗提供新的治疗策略途径。
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