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环状PTPDC1通过靶向miR-139-3p调控ELK1促进胃癌进展并作为预后生物标志物

Circ-PTPDC1 promotes the Progression of Gastric Cancer through Sponging Mir-139-3p by Regulating ELK1 and Functions as a Prognostic Biomarker.

作者信息

Li Zhouxiao, Cheng Ye, Fu Kai, Lin Qiaowei, Zhao Tianyu, Tang Weiwei, Xi Lei, Sheng Lulu, Zhang Hao, Sun Yangbai

机构信息

Department of Musculoskeletal Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai, 200032, China.

Division of Hand, Plastic and Aesthetic Surgery, University Hospital, LMU Munich, Pettenkoferstrasse 8a, 80336 Munich, Germany.

出版信息

Int J Biol Sci. 2021 Oct 17;17(15):4285-4304. doi: 10.7150/ijbs.62732. eCollection 2021.

Abstract

Circular RNAs (circRNAs) is a novel class of non-coding RNAs resulting from the non-canonical splicing of linear pre-mRNAs. However, the role of circRNAs in gastric cancer (GC) remains indistinct. This study aims to explore their potential modulation in GC and its prognostic value. We first screen for circRNA expression patterns in GC through GC and adjacent noncancerous tissues by microarray. Based on the bioinformatics analysis of the microarray data, we screened out a novel circRNA, circ-PTPDC1. Then we demonstrated that circ-PTPDC1 was up-regulated in GC cells, tissues, and serum. Its overexpression was positively correlated with age, invasion depth, advanced clinical stages, and worse survival in patients with GC. We further revealed that circ-PTPDC1 promotes the proliferation, migration, and invasion of GC cell lines via sponging miR-139-3p by regulating ELK1. Importantly, we identified that circ-PTPDC1 promotes tumor upgrowth and metabasis in vivo. Additionally, we established its prognostic prediction model based on the follow-up data of the patients. Our study revealed a novel regulatory mechanism and a comprehensive landscape of circ-PTPDC1 in GC, suggesting that circ-PTPDC1 has the potential to be a biomarker for early detection and prognostic prediction of GC.

摘要

环状RNA(circRNAs)是一类由线性前体mRNA通过非经典剪接产生的新型非编码RNA。然而,circRNAs在胃癌(GC)中的作用仍不明确。本研究旨在探讨其在GC中的潜在调控作用及其预后价值。我们首先通过微阵列技术,在GC组织及其相邻的非癌组织中筛选circRNA的表达模式。基于对微阵列数据的生物信息学分析,我们筛选出一种新型circRNA,即circ-PTPDC1。然后我们证明,circ-PTPDC1在GC细胞、组织和血清中均上调。其过表达与GC患者的年龄、浸润深度、临床晚期以及较差的生存率呈正相关。我们进一步揭示,circ-PTPDC通过调控ELK1海绵化miR-139-3p,促进GC细胞系的增殖、迁移和侵袭。重要的是,我们发现circ-PTPDC1在体内促进肿瘤生长和转移。此外,我们基于患者的随访数据建立了其预后预测模型。我们的研究揭示了circ-PTPDC1在GC中的一种新型调控机制和全面图景,表明circ-PTPDC1有潜力成为GC早期检测和预后预测的生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/69a8/8579456/2cece9efca08/ijbsv17p4285g001.jpg

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