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揭示长链非编码RNA在乳腺癌中的作用。

Unravelling the role of long non-coding RNA - in breast cancer.

作者信息

Tripathi Rashmi, Aier Imlimaong, Chakraborty Pavan, Varadwaj Pritish Kumar

机构信息

Department of Bioinformatics and Applied Sciences, Indian Institute of Information Technology-Allahabad, Allahabad, India.

Department of Information Technology, Indian Institute of Information Technology-Allahabad, Allahabad, India.

出版信息

Noncoding RNA Res. 2019 Dec 24;5(1):1-10. doi: 10.1016/j.ncrna.2019.12.002. eCollection 2020 Mar.

Abstract

Apoptosis is a 'programmed fate' of all cells participating in diverse physiological and pathological conditions. The role of critical regulators and their involvement in this complex multi-stage process of apoptosis weaved around non-coding RNAs (ncRNAs) is poorly deciphered in breast carcinoma (BC). Aberrant expression patterns of the ncRNAs and their interacting partners, either ncRNAs or coding RNAs or proteins at any point along these pathways, may lead to the malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Longest non-coding type of ncRNAs (lncRNAs) have been considered as critical factors for the development and progression of breast cancer. The aim of our study was to identify set of novel lncRNAs interacting with microRNAs (miRNAs) or proteins that were significantly dysregulated in breast cancer using RNA-Sequencing (RNA-Seq) technique in different samples acting as oncogenic drivers contributing to cancerous phenotype involved in post-transcriptional processing of RNAs. Four lncRNAs; LINC01087, lnc-CLSTN2-1:1, lnc-c7orf65-3:3 and LINC01559:2 were selected for further analysis. Gene expression analysis of over-expressed LINC01087 reduced both cell viability and apoptosis. We integrated miRNA and mRNA (hsa-miR-548 and AKT1) expression profiles with curated regulations with lncRNA (LINC01087) which has not been previously associated with any breast cancer type, using different computational tools. The network (lncRNA→ miRNA→ mRNA) is promising for the identification of carcinoma associated genes and apoptosis signaling path highlighting the potential roles of LINC01087, hsa-miR548n, AKT1 gene which may play crucial role in proliferation.

摘要

细胞凋亡是所有参与各种生理和病理状况的细胞的一种“程序性命运”。在乳腺癌(BC)中,关键调节因子的作用以及它们在围绕非编码RNA(ncRNA)的这一复杂多阶段细胞凋亡过程中的参与情况,目前仍知之甚少。ncRNA及其相互作用伙伴(无论是ncRNA、编码RNA还是蛋白质)在这些途径中任何一点的异常表达模式,都可能导致受影响细胞的恶性转化、肿瘤转移以及对抗癌药物的耐药性。最长的非编码类型ncRNA(lncRNA)被认为是乳腺癌发生和发展的关键因素。我们研究的目的是使用RNA测序(RNA-Seq)技术,在不同样本中鉴定与微小RNA(miRNA)或蛋白质相互作用的一组新型lncRNA,这些lncRNA在乳腺癌中显著失调,作为致癌驱动因子参与RNA的转录后加工过程,导致癌症表型。选择了四个lncRNA;LINC01087、lnc-CLSTN2-1:1、lnc-c7orf65-3:3和LINC01559:2进行进一步分析。过表达LINC01087的基因表达分析降低了细胞活力并诱导了细胞凋亡。我们使用不同的计算工具,将miRNA和mRNA(hsa-miR-548和AKT1)表达谱与lncRNA(LINC01087)的精心策划的调控相结合,该lncRNA以前未与任何乳腺癌类型相关联。该网络(lncRNA→miRNA→mRNA)有望用于鉴定与癌相关的基因和细胞凋亡信号通路,突出LINC01087、hsa-miR548n、AKT1基因在增殖中可能发挥的关键作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fcac/6965516/1a98b2ecb3c7/gr1.jpg

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