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构建与胰腺癌转移相关的lncRNA/假基因-hsa-miR-30d-5p-GJA1调控网络

Construction of a lncRNA/pseudogene-hsa-miR-30d-5p-GJA1 regulatory network related to metastasis of pancreatic cancer.

作者信息

Zheng Huilin, Ding Bisha, Xue Ke, Yu Jinxiao, Lou Weiyang

机构信息

School of Biological & Chemical Engineering, Zhejiang University of Science and Technology, Hangzhou 310023, Zhejiang, China.

Department of Breast Surgery, First Affiliated Hospital, College of Medicine, Zhejiang University, 79 QingChun Road, Hangzhou 310003, Zhejiang, China.

出版信息

Genomics. 2021 Jul;113(4):1742-1753. doi: 10.1016/j.ygeno.2021.04.013. Epub 2021 Apr 9.

Abstract

Pancreatic cancer, the most lethal malignant tumor, is notorious for its poor prognosis and metastatic potential. Non-coding RNAs (ncRNAs) are reported to play key roles in cancer metastasis. In this study, miRNA and gene expression profiles between metastatic pancreatic cancer cell M8 and its parental cell BxPC.3 were determined. Using differential expression analysis, survival analysis, target gene prediction, pathway enrichment analysis, intersection analysis and correlation analysis, hsa-miR-30d-5p/GJA1 axis was identified as the most potential pathway involved in metastasis of pancreatic cancer. Subsequently, two upstream lncRNAs (HELLPAR and OIP-AS1) and four upstream pseudogenes (AC093616.1, AC009951.1, TMEM183B and PABPC1P4) of hsa-miR-30d-5p/GJA1 axis were predicted and were then identified via assessment of RNA-RNA expression relationship. Furthermore, CTNNA1, CTNNB1 and CTNND1 were regarded as three crucial molecules to be participated in hsa-miR-30d-5p/GJA1-mediated metastatic potential in pancreatic cancer. In conclusion, we established a novel lncRNA/pseudogene-hsa-miR-30d-5p-GJA1 regulatory network linked to metastasis of pancreatic cancer.

摘要

胰腺癌是最致命的恶性肿瘤,因其预后不良和转移潜能而声名狼藉。据报道,非编码RNA(ncRNAs)在癌症转移中起关键作用。在本研究中,测定了转移性胰腺癌细胞M8与其亲本细胞BxPC.3之间的miRNA和基因表达谱。通过差异表达分析、生存分析、靶基因预测、通路富集分析、交集分析和相关性分析,hsa-miR-30d-5p/GJA1轴被确定为参与胰腺癌转移的最具潜力的通路。随后,预测了hsa-miR-30d-5p/GJA1轴的两个上游lncRNA(HELLPAR和OIP-AS1)和四个上游假基因(AC093616.1、AC009951.1、TMEM183B和PABPC1P4),并通过评估RNA-RNA表达关系对其进行了鉴定。此外,CTNNA1、CTNNB1和CTNND1被认为是参与hsa-miR-30d-5p/GJA1介导的胰腺癌转移潜能的三个关键分子。总之,我们建立了一个与胰腺癌转移相关的新型lncRNA/假基因-hsa-miR-30d-5p-GJA1调控网络。

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