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miRNA-27a 与胃癌新辅助化疗疗效的关系及其对胃癌细胞生长和转移的作用机制。

Relationship between microRNA-27a and efficacy of neoadjuvant chemotherapy in gastric cancer and its mechanism in gastric cancer cell growth and metastasis.

机构信息

Department of Digestive Internal Medicine, The Affiliated Tumor Hospital of Xinjiang Medical University, Wunumuqi 830053, P.R. China.

Department of Laboratory, The Affiliated Tumor Hospital of Xinjiang Medical University, Wunumuqi 830053, P.R. China.

出版信息

Biosci Rep. 2019 May 21;39(5). doi: 10.1042/BSR20181175. Print 2019 May 31.

Abstract

The aim of the present study is to investigate the relationship between microRNA-27a (miR-27a) and the efficacy of neoadjuvant chemotherapy in gastric cancer (GC) and its mechanism in the growth and metastasis of GC cells. The expression of miR-27a in serum of 74 GC patients received neoadjuvant chemotherapy was detected by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). Clinical value and prognosis of miR-27a expression in predicting the efficacy of neoadjuvant chemotherapy in GC were evaluated. Besides, GC cells with low miR-27a expression were transfected with miR-27a mimics, and cells with high miR-27a expression were transfected with miR-27a inhibitors and secreted frizzled-related protein 1 (SFRP1) siRNA. A series of experiments were applied for the determination of cell viability, invasion and migration of GC cells. After neoadjuvant chemotherapy, the expression of miR-27a in serum of GC patients decreased significantly. Additionally, the expression of miR-27a in GC cell line was significantly higher than that in normal gastric mucosa cell line. Meanwhile, after down-regulating the expression of miR-27a in GC cells, the mRNA and protein expression of SFRP1 increased, the proliferation rate of cells slowed down, and the ability of invasion and migration decreased. Furthermore, combined with low expression of miR-27a and SFRP1, the proliferation rate of GC cells increased and the ability of invasion and migration increased. Collectively, our study highlights that the high expression of miR-27a indicates the poor efficacy and prognosis of neoadjuvant chemotherapy in GC patients. Down-regulation of miR-27a can inhibit the growth and metastasis of GC cells via up-regulation of SFRP1.

摘要

本研究旨在探讨微小 RNA-27a(miR-27a)与胃癌(GC)新辅助化疗疗效的关系及其在 GC 细胞生长和转移中的机制。采用实时定量逆转录聚合酶链反应(qRT-PCR)检测 74 例接受新辅助化疗的 GC 患者血清中 miR-27a 的表达。评估 miR-27a 表达预测 GC 新辅助化疗疗效的临床价值和预后。此外,用 miR-27a 模拟物转染 miR-27a 低表达的 GC 细胞,用 miR-27a 抑制剂和卷曲相关蛋白 1(SFRP1)siRNA 转染 miR-27a 高表达的 GC 细胞,并进行一系列实验以测定 GC 细胞的活力、侵袭和迁移。新辅助化疗后,GC 患者血清中 miR-27a 的表达明显降低。此外,GC 细胞系中的 miR-27a 表达明显高于正常胃黏膜细胞系。同时,下调 GC 细胞中 miR-27a 的表达后,SFRP1 的 mRNA 和蛋白表达增加,细胞增殖速度减慢,侵袭和迁移能力下降。此外,结合 miR-27a 和 SFRP1 的低表达,GC 细胞的增殖速度加快,侵袭和迁移能力增强。综上所述,本研究表明 miR-27a 的高表达预示着 GC 患者新辅助化疗疗效不佳且预后不良。下调 miR-27a 可通过上调 SFRP1 抑制 GC 细胞的生长和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c4a/6527950/ad1d324b2609/bsr-39-bsr20181175-g1.jpg

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