通过RNA测序鉴定腔面A型乳腺癌的关键长链非编码RNA
Identification of Crucial lncRNAs for Luminal A Breast Cancer through RNA Sequencing.
作者信息
Jia Xinjian, Lei Hai, Jiang Xuemei, Yi Ying, Luo Xue, Li Junyan, Chen Yu, Liu Sha, Yang Chengcheng
机构信息
Department of Breast Surgery, Deyang People's Hospital, Deyang, Sichuan Province, China.
出版信息
Int J Endocrinol. 2022 Jun 2;2022:6577942. doi: 10.1155/2022/6577942. eCollection 2022.
BACKGROUND
The growing body of evidence indicates aberrant expression of long noncoding RNAs (lncRNAs) in breast cancer. Nevertheless, a few studies have focused on identifying key lncRNAs for patients with luminal A breast cancer. In our study, we tried to find key lncRNAs and mRNAs in luminal A breast cancer.
METHODS
RNA sequencing was performed to identify differentially expressed mRNAs (DEmRNAs) and differentially expressed lncRNAs (DElncRNAs) in luminal A breast cancer. The protein-protein interaction (PPI), DElncRNA-DEmRNA coexpression, DElncRNA-nearby DEmRNA interaction networks, and functional annotation were performed to uncover the function of DEmRNAs. Online databases were used to validate the RNA sequencing result. The diagnostic value of candidate mRNAs was evaluated by receiver operating characteristic (ROC) curve analysis.
RESULTS
A total number of 1451 DEmRNAs and 272 DElncRNAs were identified. Several hub proteins were identified in the PPI network, including TUBB3, HIST2H3C, MCM2, MYOC, NEK2, LIPE, FN1, FOXJ1, S100A7, and DLK1. In the DElncRNA-DEmRNA coexpression, some hub lncRNAs were identified, including AP001528.2, LINC00968, LINC02202, TRHDE-AS1, LINC01140, AL354707.1, AC097534.1, MIR222HG, and AL662844.4. The mRNA expression result of TFF1, COL10A1, LEP, PLIN1, PGM5-AS1, and TRHDE-AD1 in the GSE98793 was consistent with the RNA sequencing result. The protein expression results of TUBB3, MCM2, MYOC, FN1, S100A7, and TFF1 were consistent with the mRNA expression result COL10A1, LEP, PLIN1, PGM5-AS1, and TRHDE-AD1 were capable of discriminating luminal A breast cancer and normal controls. Four lncRNA-nearby and coexpressed mRNA pairs of HOXC-AS3-HOXC10, AC020907.2-FXYD1, AC026461.1-MT1X, and AC132217.1-IGF2 were identified. AMPK (involved LIPE and LEP) and PPAR (involved PLIN1) were two significantly enriched pathways in luminal A breast cancer.
CONCLUSION
This study could be helpful in unraveling the pathogenesis and providing novel therapeutic strategies for luminal A breast cancer.
背景
越来越多的证据表明长链非编码RNA（lncRNA）在乳腺癌中表达异常。然而，很少有研究专注于鉴定腔面A型乳腺癌患者的关键lncRNA。在我们的研究中，我们试图寻找腔面A型乳腺癌中的关键lncRNA和mRNA。
方法
进行RNA测序以鉴定腔面A型乳腺癌中差异表达的mRNA（DEmRNA）和差异表达的lncRNA（DElncRNA）。进行蛋白质-蛋白质相互作用（PPI）、DElncRNA-DEmRNA共表达、DElncRNA-邻近DEmRNA相互作用网络和功能注释以揭示DEmRNA的功能。使用在线数据库验证RNA测序结果。通过受试者工作特征（ROC）曲线分析评估候选mRNA的诊断价值。
结果
共鉴定出1451个DEmRNA和272个DElncRNA。在PPI网络中鉴定出几个枢纽蛋白，包括TUBB3、HIST2H3C、MCM2、MYOC、NEK2、LIPE、FN1、FOXJ1、S100A7和DLK1。在DElncRNA-DEmRNA共表达中，鉴定出一些枢纽lncRNA，包括AP001528.2、LINC00968,、LINC02202、TRHDE-AS1、LINC01140、AL354707.1、AC097534.1、MIR222HG和AL662844.4。GSE98793中TFF1、COL10A1、LEP、PLIN1、PGM5-AS1和TRHDE-AD1的mRNA表达结果与RNA测序结果一致。TUBB3、MCM2、MYOC、FN1、S100A7和TFF1的蛋白质表达结果与mRNA表达结果一致。COL10A1、LEP、PLIN1、PGM5-AS1和TRHDE-AD1能够区分腔面A型乳腺癌和正常对照。鉴定出HOXC-AS3-HOXC10、AC020907.2-FXYD1、AC026461.1-MT1X和AC132217.1-IGF2这四对lncRNA-邻近且共表达的mRNA。AMPK（涉及LIPE和LEP）和PPAR（涉及PLIN1）是腔面A型乳腺癌中两个显著富集的通路。
结论
本研究有助于阐明腔面A型乳腺癌的发病机制并提供新的治疗策略。
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