miR-661 通过直接抑制非小细胞肺癌中的 RB1 促进肿瘤侵袭和转移。
MiR-661 promotes tumor invasion and metastasis by directly inhibiting RB1 in non small cell lung cancer.
机构信息
Cancer Center, Traditional Chinese Medicine-Integrated Hospital, Southern medical University, Guangdong, 510315, China.
Center for Geriatrics, General Hospital of Guangzhou Military Command of People's Liberation Army, Guangdong, 510010, China.
出版信息
Mol Cancer. 2017 Jul 17;16(1):122. doi: 10.1186/s12943-017-0698-4.
BACKGROUND
Aberrant microRNA expression has been implicated in metastasis of cancers. MiR-661 accelerates proliferation and invasion of breast cancer and ovarian cancer, while impedes that of glioma. Its role in non small cell lung cancer (NSCLC) and underlying mechanism are worthy elucidation.
METHODS
Expression of miR-661 was measured with real-time PCR in both NSCLC tissues and cell lines. The effects of miR-661 on migration, invasion and metastasis capacity of NSCLC were evaluated using wound healing, transwell assay and animal models. Dual reporter luciferase assay and complementary experiments were performed to validate RB1 as a direct target of miR-661 for participation in the progression of NSCLC.
RESULTS
MiR-661 was upregulated in NSCLC tissues as compared to paired adjacent tissues and associated with shorter overall survival. Furthermore, miR-661 promoted proliferation, migration and metastasis of NSCLC. Then, we identified RB1 as a direct target of miR-661 through which miR-661 affected EMT process and metastasis of NSCLC. RB1 interacted with E2F1 and both could mediate EMT process in NSCLC.
CONCLUSION
MiR-661 promotes metastasis of NSCLC through RB/E2F1 signaling and EMT events, thus may serves as a negative prognostic factor and possible target for treatment of NSCLC patient.
背景
异常的 microRNA 表达与癌症的转移有关。miR-661 促进乳腺癌和卵巢癌的增殖和侵袭，而抑制神经胶质瘤的增殖和侵袭。其在非小细胞肺癌（NSCLC）中的作用及其潜在机制值得阐明。
方法
采用实时 PCR 检测 NSCLC 组织和细胞系中 miR-661 的表达。通过划痕愈合、Transwell 测定和动物模型评估 miR-661 对 NSCLC 迁移、侵袭和转移能力的影响。双荧光素酶报告基因检测和互补实验验证 RB1 是 miR-661 的直接靶基因，参与 NSCLC 的进展。
结果
与配对的相邻组织相比，miR-661 在 NSCLC 组织中上调，与总生存期缩短相关。此外，miR-661 促进了 NSCLC 的增殖、迁移和转移。然后，我们通过 miR-661 影响 EMT 过程和 NSCLC 转移来确定 RB1 是 miR-661 的直接靶基因。RB1 与 E2F1 相互作用，两者均可介导 NSCLC 中的 EMT 过程。
结论
miR-661 通过 RB/E2F1 信号和 EMT 事件促进 NSCLC 的转移，因此可能作为 NSCLC 患者的预后不良因素和可能的治疗靶点。
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