ABSTRACT

Objective

Since the essential involvement of microRNAs (miRNAs) in the development and progression of GC, the study was for the exploration of the value of microRNA-7 (miR-7) in the evaluation of neoadjuvant chemotherapy for gastric cancer (GC) and its effects on apoptosis, proliferation and angiogenesis of GC.

Methods

miR-7 expression in serum of GC patients before and after neoadjuvant chemotherapy were detected to explore its role in neoadjuvant chemotherapy of GC. The GC cells were transfected with miR-7 mimics/inhibitors, or siRNA-Raf-1 to figure out their roles in proliferation, migration, invasion, cycle distribution and apoptosis. Tumor xenograft was conducted to test tumor growth. Microvessel density (MVD) in tumors was tested by immunohistochemical staining.

Results

miR-7 expression in serum of GC patients was lower than that of healthy controls while it was elevated after neoadjuvant chemotherapy. Moreover, higher miR-7 expression was exhibited in chemotherapy-effective patients rather than chemotherapy-ineffective patients (P < 0.01). miR-7 expression in serum was connected with tumor size, degree of differentiation, TNM stage and lymphatic metastasis.miR-7 was decreased and Raf-1 was elevated in GC cells (both P < 0.05). Elevated miR-7 or declined Raf-1 inhibited GC cell migration, proliferation and invasion, cell cycle entry, xenografted tumor growth and MVD and stimulated apoptosis (all P < 0.05). Down-regulated Raf-1 reversed the impacts of miR-7 knockdown on GC cells (all P < 0.05).

Conclusion

Our study highlights that elevated miR-27a indicates the good efficacy of neoadjuvant chemotherapy in GC and miR-7 targets Raf-1 to suppress tumor development and angiogenesis of GC cells.

中文翻译：

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升高的 microRNA-7 通过抑制 Raf-1 抑制增殖和肿瘤血管生成并促进胃癌细胞凋亡。

摘要

客观的

由于microRNAs（miRNAs）在GC的发生发展过程中必不可少，本研究旨在探讨microRNA-7（miR-7）在胃癌（GC）新辅助化疗评估及其疗效中的价值GC 的凋亡、增殖和血管生成。

方法

检测胃癌患者新辅助化疗前后血清中miR-7的表达,探讨其在胃癌新辅助化疗中的作用。GC 细胞用 miR-7 模拟物/抑制剂或 siRNA-Raf-1 转染，以确定它们在增殖、迁移、侵袭、周期分布和细胞凋亡中的作用。进行肿瘤异种移植以测试肿瘤生长。通过免疫组织化学染色测试肿瘤中的微血管密度（MVD）。

结果

胃癌患者血清中 miR-7 的表达低于健康对照，而在新辅助化疗后升高。此外，化疗有效患者中miR-7表达高于化疗无效患者（P < 0.01）。血清中miR-7的表达与肿瘤大小、分化程度、TNM分期和淋巴转移有关。GC细胞中miR-7降低，Raf-1升高（均P < 0.05）。升高的 miR-7 或降低的 Raf-1 抑制 GC 细胞迁移、增殖和侵袭、细胞周期进入、异种移植肿瘤生长和 MVD 并刺激细胞凋亡（均P < 0.05）。下调的 Raf-1 逆转了 miR-7 敲低对 GC 细胞的影响（所有P < 0.05）。

结论

我们的研究强调，升高的 miR-27a 表明新辅助化疗在 GC 中的良好疗效，并且 miR-7 靶向 Raf-1 以抑制 GC 细胞的肿瘤发展和血管生成。