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Low expression of miR-let-7a promotes cell growth and invasion through the regulation of c-Myc in oral squamous cell carcinoma.
Cell Cycle ( IF 3.4 ) Pub Date : 2020-06-28 , DOI: 10.1080/15384101.2020.1786633
Chunyang Luo 1 , Jiyong Zhang 1 , Yi Zhang 1 , Xiao Zhang 1 , Yinan Chen 2 , Weimin Fan 1
Affiliation  

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.



中文翻译:


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



在口腔鳞状细胞癌(OSCC)中,microRNA 的异常表达已被广泛报道。 MiR-let-7a已被证实是多种癌症的关键调节因子,但其所涉及的生物学过程及其在OSCC中的潜在作用仍不清楚。我们首先分析了miR-let-7a在癌组织、癌旁非癌组织和癌组织中的差异表达。细胞系。通过体外集落形成测定、细胞增殖和 Transwell 侵袭测定评估 miR-let-7a 在 OSCC 细胞系中的功能作用。此外,将转染miR-let-7a的细胞皮下异种移植到裸鼠模型中,以探讨miR-let-7a在体内的潜在功能。发现与相比,miR-let-7a在OSCC组织中的水平显着下调与匹配的正常组织 (n = 60) 相比,miR-let-7a 的低表达与 OSCC 患者的不良预后相关。在裸鼠模型中,MiR-let-7a 的过表达可抑制增殖、侵袭和迁移,并抑制肿瘤发生。我们还确定 c-Myc 可能作为 miR-let-7a 的直接靶标;此外,上调的c-Myc表达可以部分缓解miR-let-7a过表达引起的影响。 miR-let-7a 在 OSCC 中低表达,通过直接靶向 c-Myc 促进肿瘤发展。我们的结果可能为 miR-let-7a 在人类 OSCC 中发挥潜在的治疗作用。

更新日期:2020-07-27
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