MicroRNA-221-3p promotes cell proliferation, migration, and invasion in gastric cancer by modulating PIK3R1

Q3 Biochemistry, Genetics and Molecular Biology
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Abstract

Background: Gastric cancer (GC), which is the fourth most prevalent cancer in the world is significantly threatened the health of people, particularly those in developing nations. Nearly all significant pathological and physiological mechanisms, including apoptosis, proliferation, cell cycle, differentiation, as well as DNA damage, are regulated by miRNAs. This study looked at the miR-221-3p expression and to identified it's target genes in GC tissue specimens and cell lines, to comprehend the miR-221-3p influence in the development of GC. Methods: GC tissues and matched marginal tissues were taken from 50 patients undergo gastric surgery. MiR-221-3p mimics, inhibitors and negative controls (NC) were transfected into MKN-45 cells, using Lipofectamine RNAiMAX reagent. The proliferation was assessed by the MTT assay. Cell migration and invasion was assessed by Transwell assay. By combining Western blotting and qRT-PCR, the impact of miR-221-3p in the PIK3R1 expression in gastric cancer cells was examined. Results: Overexpression of miR-221-3p significantly enhanced the migration, invasion and proliferation of gastric cancer cells, conversely, transfection of miR-221-3p inhibitor led to opposite effect caused by overexpression of this miRNA on phenotypic characteristics of gastric cancer cell line. Additional investigation revealed that PIK3R1 was downregulated significantly by overexpression of miR-221-3p. Whereas, when the MKN-45 cells transfected with miR-221-3p inhibitor, PIK3R1 was noticeably overexpressed. Conclusions: Our current data indicate that miR-221-3p possibly work as a tumor promoter in the development of gastric cancer by negatively regulating PIK3R1 expression, hence miR-221-3p/ PIK3R1 highlighted as promising therapeutic targets or prognostic and diagnostic biomarkers for GC patients.
MicroRNA-221-3p通过调节PIK3R1促进胃癌细胞增殖、迁移和侵袭
背景:胃癌(GC)是世界上第四大常见癌症,严重威胁着人们的健康,特别是在发展中国家。几乎所有重要的病理和生理机制,包括细胞凋亡、增殖、细胞周期、分化以及DNA损伤,都受到mirna的调控。本研究通过观察miR-221-3p在胃癌组织标本和细胞系中的表达并鉴定其靶基因,了解miR-221-3p在胃癌发生发展中的影响。方法:取50例胃手术患者的胃癌组织及相匹配的边缘组织。使用Lipofectamine RNAiMAX试剂将MiR-221-3p模拟物、抑制剂和阴性对照(NC)转染到MKN-45细胞中。MTT法测定细胞增殖情况。Transwell法检测细胞迁移和侵袭。结合Western blotting和qRT-PCR检测miR-221-3p对胃癌细胞中PIK3R1表达的影响。结果:过表达miR-221-3p可显著增强胃癌细胞的迁移、侵袭和增殖,反之,转染miR-221-3p抑制剂可导致过表达该miRNA对胃癌细胞系表型特征的相反影响。进一步的研究发现,PIK3R1通过miR-221-3p的过表达而显著下调。然而,当转染miR-221-3p抑制剂的MKN-45细胞中,PIK3R1明显过表达。结论:我们目前的数据表明,miR-221-3p可能通过负调控PIK3R1的表达而在胃癌的发展中起到肿瘤启动子的作用,因此miR-221-3p/ PIK3R1被强调为胃癌患者有希望的治疗靶点或预后和诊断生物标志物。
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来源期刊
Journal of Advanced Biotechnology and Experimental Therapeutics
Journal of Advanced Biotechnology and Experimental Therapeutics Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (all)
CiteScore
1.90
自引率
0.00%
发文量
41
审稿时长
8 weeks
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