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微小RNA-28-5p通过抑制AKT磷酸化来抑制胃癌细胞的迁移和侵袭。

MicroRNA-28-5p inhibits the migration and invasion of gastric cancer cells by suppressing AKT phosphorylation.

作者信息

Xiao Fangtao, Cheng Zhenguo, Wang Pengliang, Gong Baoheng, Huang Hanwei, Xing Yanan, Liu Funan

机构信息

Department of Surgical Oncology and General Surgery, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Department of Cell Biology, Key Laboratory of Cell Biology, Ministry of Public Health, and Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, Liaoning 110001, P.R. China.

出版信息

Oncol Lett. 2018 Jun;15(6):9777-9785. doi: 10.3892/ol.2018.8603. Epub 2018 Apr 27.

Abstract

Gastric cancer is a polygenic disease with a high mortality rate worldwide. Although a number of dysregulated genes have been confirmed to be involved in development and progression of gastric cancer, the molecular mechanisms by which this occurs remain unclear. The present study identified that microRNA (miR-28-5p) was involved in the migration and invasion of gastric cancer cells, and was able to affect the prognosis of patients with gastric cancer. Reverse transcription-quantitative polymerase chain reaction analysis indicated that the expression of miR-28-5p was significantly downregulated in gastric cancer tissues, and that patients with higher expression had a good prognosis. miR-28-5p expression was significantly associated with depth of invasion, lymph node metastasis and pathological stage. Gastric cancer cells overexpressing miR-28-5p exhibited a marked reduction of migration and invasion by Transwell and wound scratch assay. The phosphorylation of RAC serine/threonine-protein kinase (AKT), which affected cellular invasion and metastasis, was significantly inhibited by overexpression of miR-28-5p. In conclusion, miR-28-5p is a tumor suppressor that inhibits gastric cancer cell migration and invasion through repressing AKT phosphorylation. miR-28-5p may therefore represent a potential biomarker for the prognosis of gastric cancer and a novel therapeutic target in advanced gastric cancer.

摘要

胃癌是一种多基因疾病,在全球范围内死亡率很高。尽管已证实一些失调基因参与胃癌的发生和发展,但其发生的分子机制仍不清楚。本研究发现,微小RNA(miR-28-5p)参与胃癌细胞的迁移和侵袭,并能够影响胃癌患者的预后。逆转录-定量聚合酶链反应分析表明,miR-28-5p在胃癌组织中的表达显著下调,表达较高的患者预后良好。miR-28-5p表达与浸润深度、淋巴结转移和病理分期显著相关。通过Transwell和划痕试验,过表达miR-28-5p的胃癌细胞迁移和侵袭明显减少。影响细胞侵袭和转移的RAC丝氨酸/苏氨酸蛋白激酶(AKT)的磷酸化被miR-28-5p的过表达显著抑制。总之,miR-28-5p是一种肿瘤抑制因子,通过抑制AKT磷酸化来抑制胃癌细胞的迁移和侵袭。因此,miR-28-5p可能是胃癌预后的潜在生物标志物和晚期胃癌的新型治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f17/6004724/055593186b52/ol-15-06-9777-g00.jpg

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