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miR-let-7a 低表达通过调节 c-Myc 促进口腔鳞状细胞癌的细胞生长和侵袭。

Low expression of miR-let-7a promotes cell growth and invasion through the regulation of c-Myc in oral squamous cell carcinoma.

机构信息

Department of Orthopaedics, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China.

Department of Anesthesiology, The First Affiliated Hospital of Nanjing Medical University , Nanjing, China.

出版信息

Cell Cycle. 2020 Aug;19(15):1983-1993. doi: 10.1080/15384101.2020.1786633. Epub 2020 Jun 28.

Abstract

In oral squamous cell carcinoma (OSCC), abnormal expression of microRNAs has been extensively reported. MiR-let-7a has been validated as a critical regulator of multiple cancers, but the biological process involved and its potential role in OSCC remain unknown.We first analyzed the differential expression of miR-let-7a in cancer tissues, adjacent noncancerous tissues and cell lines. The functional role of miR-let-7a in OSCC cell lines was evaluated by using colony formation assays, cell proliferation and transwell invasion assays in vitro. In addition, subcutaneous xenotransplantation of miR-let-7a transfected cells into nude mouse model was carried out to explore the potential function of miR-let-7a in vivo.miR-let-7a levels were found to be significantly downregulated in OSCC tissues compared with matched normal tissues (n = 60), and lower expression of miR-let-7a was related to poor prognosis in OSCC patients. Overexpression of MiR-let-7a induced a suppression in proliferation, invasion and migration and inhibited tumourigenesis in the nude mouse model. We also determined that c-Myc may serve as a direct target of miR-let-7a; furthermore, upregulated c-Myc expression could partially rescue the effects caused by miR-let-7a overexpression. miR-let-7a is low expression in OSCC, and promotes tumor development by directly targeting c-Myc. Our results may provide a potential therapeutic role for miR-let-7a in human OSCC.

摘要

在口腔鳞状细胞癌(OSCC)中,已广泛报道微小 RNA 的异常表达。miR-let-7a 已被验证为多种癌症的关键调节因子,但涉及的生物学过程及其在 OSCC 中的潜在作用尚不清楚。

我们首先分析了 miR-let-7a 在癌症组织、相邻非癌组织和细胞系中的差异表达。通过体外集落形成试验、细胞增殖和 Transwell 侵袭试验评估了 miR-let-7a 在 OSCC 细胞系中的功能作用。此外,还通过将转染了 miR-let-7a 的细胞进行皮下异种移植到裸鼠模型中,来探讨 miR-let-7a 在体内的潜在功能。

与匹配的正常组织(n=60)相比,OSCC 组织中 miR-let-7a 的水平明显下调,miR-let-7a 的低表达与 OSCC 患者的不良预后相关。过表达 miR-let-7a 可抑制裸鼠模型中的增殖、侵袭和迁移,并抑制肿瘤发生。我们还确定 c-Myc 可能是 miR-let-7a 的直接靶标;此外,上调 c-Myc 表达可部分挽救 miR-let-7a 过表达引起的效应。

miR-let-7a 在 OSCC 中低表达,通过直接靶向 c-Myc 促进肿瘤的发展。我们的研究结果可能为 miR-let-7a 在人类 OSCC 中的治疗作用提供了一种潜在的作用机制。

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