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作为胃癌的生物标志物,环状PTPN22通过上皮-间质转化途径调节胃癌的进展。

As a biomarker for gastric cancer, circPTPN22 regulates the progression of gastric cancer through the EMT pathway.

作者信息

Ma Shuo, Kong Shan, Gu Xinliang, Xu Yanhua, Tao Mei, Shen Lei, Shen Xianjuan, Ju Shaoqing

机构信息

Department of Laboratory Medicine, Affiliated Hospital of Nantong University, Xisi Road, No. 20, Nantong, 226001, Jiangsu, China.

Research Center of Clinical Medicine, Affiliated Hospital of Nantong University, Nantong, 226001, Jiangsu, China.

出版信息

Cancer Cell Int. 2021 Jan 11;21(1):44. doi: 10.1186/s12935-020-01701-1.

DOI:10.1186/s12935-020-01701-1
PMID:33430866
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7802183/
Abstract

BACKGROUND

Gastric cancer (GC) is one of the most common cancers in the world. Due to the lack of specific symptoms, more than 80% of patients are diagnosed as the advanced stage with a high mortality rate, so the early diagnosis of GC is incredibly essential. Circular RNAs (CircRNAs) are a kind of endogenous non-coding RNA with stable structure, the long half-life, and tumor specificity. It can be used as a diagnostic marker for tumors.

METHOD

Using circRNA sequencing technology screened three pairs of GC and adjacent tissues, and circRNAs with significant expression differences were screened out. The circular structure and characteristics of circPTPN22 were determined by RT-qPCR, agarose gel electrophoresis, Sanger sequencing, RNase R, and actinomycin D assays. Cell Counting Kit-8, colony formation, Transwell, Wound healing, tumor formation in mice and western blotting assays were used to detect the effects of circPTPN22 on the proliferation, invasion, migration, tumor growth of GC cells in vitro and protein expression.

RESULT

CircPTPN22 is up-regulated and positively correlated with metastasis in GC tissues, cells, and plasma. RT-qPCR results showed that circPTPN22 had good diagnostic efficacy and could be used to predict the prognosis of GC patients. In vitro and vivo experiments showed that the downregulation of circPTPN22 could inhibit cell proliferation, migration, and invasion through the epithelial-mesenchymal transformation (EMT) pathway. CircPTPN22 may regulate GC progression through the competitive binding of miRNAs.

CONCLUSION

CircPTPN22 can be used as a potential diagnostic and prognostic marker for GC and can inhibit cell proliferation and metastasis through the competitive binding of miRNA to inhibit the EMT pathway.

摘要

背景

胃癌(GC)是世界上最常见的癌症之一。由于缺乏特异性症状,超过80%的患者被诊断为晚期,死亡率很高,因此胃癌的早期诊断极其重要。环状RNA(CircRNAs)是一种内源性非编码RNA,具有结构稳定、半衰期长和肿瘤特异性的特点。它可以用作肿瘤的诊断标志物。

方法

利用环状RNA测序技术筛选三对胃癌组织和癌旁组织,筛选出表达差异显著的环状RNA。通过RT-qPCR、琼脂糖凝胶电泳、桑格测序、RNase R和放线菌素D试验确定circPTPN22的环状结构和特征。采用细胞计数试剂盒-8、集落形成、Transwell、伤口愈合、小鼠肿瘤形成和蛋白质印迹试验检测circPTPN22对胃癌细胞体外增殖、侵袭、迁移、肿瘤生长及蛋白质表达的影响。

结果

circPTPN22在胃癌组织、细胞和血浆中上调,且与转移呈正相关。RT-qPCR结果显示circPTPN22具有良好的诊断效能,可用于预测胃癌患者的预后。体外和体内实验表明,circPTPN22的下调可通过上皮-间质转化(EMT)途径抑制细胞增殖、迁移和侵袭。circPTPN22可能通过与微小RNA(miRNAs)的竞争性结合来调节胃癌进展。

结论

circPTPN22可作为胃癌潜在的诊断和预后标志物,并可通过与miRNA的竞争性结合抑制EMT途径来抑制细胞增殖和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/3ba94c957da2/12935_2020_1701_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/b18d1d7d5783/12935_2020_1701_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/1b909e6a25fb/12935_2020_1701_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/0b1a6513b75f/12935_2020_1701_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/0beeb5523d2a/12935_2020_1701_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/773d245cf5bf/12935_2020_1701_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/0599c8350756/12935_2020_1701_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/3ba94c957da2/12935_2020_1701_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/b18d1d7d5783/12935_2020_1701_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/1b909e6a25fb/12935_2020_1701_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/0b1a6513b75f/12935_2020_1701_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/0beeb5523d2a/12935_2020_1701_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/773d245cf5bf/12935_2020_1701_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/0599c8350756/12935_2020_1701_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0307/7802183/3ba94c957da2/12935_2020_1701_Fig7_HTML.jpg

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