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环状RNA_100395的上调通过靶向PI3K/AKT轴海绵化miR-142-3p来抑制胃癌进展。

Upregulation of circRNA_100395 sponges miR-142-3p to inhibit gastric cancer progression by targeting the PI3K/AKT axis.

作者信息

Cheng Zhiyi, Liu Guiyuan, Huang Chuanjiang, Zhao Xiaojun

机构信息

Department of Gastrointestinal Surgery, Hospital Affiliated 5 to Nantong University, Taizhou People's Hospital, Taizhou, Jiangsu 225300, P.R. China.

出版信息

Oncol Lett. 2021 May;21(5):419. doi: 10.3892/ol.2021.12680. Epub 2021 Mar 28.

DOI:10.3892/ol.2021.12680
PMID:33841580
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8020390/
Abstract

Gastric cancer (GC) has a high morbidity and mortality, hence it is very important to elucidate the molecular pathogenesis mechanism of GC progression in order to find new treatment strategies. The present study aimed to explore the biological function of circular RNA_100395 (circRNA_100395) in GC. The expression level of circRNA_100395 in GC tissues, as well as normal epithelial cells and various gastric cancer cell lines, was detected using reverse transcription-quantitative PCR. Cell Counting Kit-8, EdU assay, flow cytometry and Transwell assays were performed to investigate cell proliferation, apoptosis, migration and invasion, respectively. A dual-luciferase reporter assay was performed to detect the correlation between circRNA_100395 and micro (mi)RNA-142-3p. Western blotting was performed to elucidate the potential regulatory mechanism. circRNA_100395 expression was found to be increased in GC tissues and cell lines. However, miR-142-3p expression was significantly reduced. Besides, low expression levels of circRNA_100395 were associated with poor tumor differentiation, advanced Tumor-Node-Metastasis stage, lymph node metastasis and shorter overall survival time. Moreover, overexpression of circRNA_100395 suppressed cell proliferation, increased the apoptosis rate and suppressed cell invasion and migration by inhibiting the PI3K/AKT signaling pathway. These findings also showed that miRNA-142-3p rescued the antitumor effects induced by circRNA_100395-overexpression. cirRNA_100395-overexpression had antitumor effects via regulating the miR-142-3p signaling pathway, which might be a promising treatment target for GC.

摘要

胃癌(GC)的发病率和死亡率都很高,因此阐明胃癌进展的分子发病机制对于寻找新的治疗策略非常重要。本研究旨在探讨环状RNA_100395(circRNA_100395)在胃癌中的生物学功能。采用逆转录定量PCR检测circRNA_100395在胃癌组织、正常上皮细胞和各种胃癌细胞系中的表达水平。分别进行细胞计数试剂盒-8、EdU检测、流式细胞术和Transwell检测,以研究细胞增殖、凋亡、迁移和侵袭情况。进行双荧光素酶报告基因检测以检测circRNA_100395与微小(mi)RNA-142-3p之间的相关性。采用蛋白质免疫印迹法阐明潜在的调控机制。发现circRNA_100395在胃癌组织和细胞系中的表达增加。然而,miR-142-3p的表达显著降低。此外,circRNA_100395低表达与肿瘤分化差、肿瘤-淋巴结-转移分期晚、淋巴结转移和总生存时间短有关。此外,circRNA_100395的过表达通过抑制PI3K/AKT信号通路抑制细胞增殖,增加凋亡率,并抑制细胞侵袭和迁移。这些发现还表明,miRNA-142-3p挽救了circRNA_100395过表达诱导的抗肿瘤作用。circRNA_100395过表达通过调节miR-142-3p信号通路发挥抗肿瘤作用,这可能是胃癌一个有前景的治疗靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/420709bbd8ba/ol-21-05-12680-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/0d3ac72e2642/ol-21-05-12680-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/bf3db2a6c39b/ol-21-05-12680-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/43cd7b30f4af/ol-21-05-12680-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/ad4a62a415d0/ol-21-05-12680-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/33b1aab501c7/ol-21-05-12680-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/420709bbd8ba/ol-21-05-12680-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/0d3ac72e2642/ol-21-05-12680-g00.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/bf3db2a6c39b/ol-21-05-12680-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/43cd7b30f4af/ol-21-05-12680-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/ad4a62a415d0/ol-21-05-12680-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/33b1aab501c7/ol-21-05-12680-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2292/8020390/420709bbd8ba/ol-21-05-12680-g05.jpg

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