Lymphatic metastasis-associated circRNA‒miRNA‒mRNA network for exploring the pathogenesis and therapeutic target of triple negative breast cancer based on whole-transcriptome sequencing analysis: an experimental verification study.
Lymphatic metastasis-associated circRNA‒miRNA‒mRNA network for exploring the pathogenesis and therapeutic target of triple negative breast cancer based on whole-transcriptome sequencing analysis: an experimental verification study.
复制标题
DOI：
10.1186/s12967-022-03728-6
复制
发表时间：
2022-11-05
影响因子：
7.4
通讯作者：
Lai, Jianguo
中科院分区：
文献类型：
--
作者：
Luo, Jiayue;Cao, Dong;Hu, Chuwen;Liang, Zhen;Zhang, Yuanping;Lai, Jianguo
关键词：
三阴性乳腺癌（TNBC）腋窝淋巴结（ALN）的转移机制尚不清楚。我们的目的是确定ALN转移中潜在的circRNA调控网络。我们进行了全转录组测序（WTS），以确定RNA的表达谱，并筛选出ALN阳性和ALN阴性TNBC患者之间差异表达的信使RNA（DEM）、微小RNA（DEM）和circRNA（德克斯）。利用功能富集分析和Kaplan-Meier生存分析来揭示DEM的潜在调节机制。利用计算生物学构建了竞争性内源RNA（ceRNA）网络。通过实时荧光定量PCR（RT-PCR）证实细胞系中德克斯的表达水平。在WTS和差异表达分析之后，在ALN阳性和ALN阴性TNBC患者之间鉴定了739个DEM、110个DEM和206个德克斯。功能分析表明，DEMs主要在肿瘤发生和肿瘤进展相关通路中发挥作用。开发了包含8个circRNA、6个miRNA和18个mRNA的ceRNA网络。在ceRNA网络中，选择与TNBC患者中更好的总生存率显著相关的两种mRNA（RAB 3D和EDARADD）和预测有利的无复发生存率的一种mRNA（GSR）用于进一步分析。然后，鉴定了包含两个德克斯（hsa_circ_0061260和hsa_circ_0060876）、两个DEM（hsa-miR-5000- 3 p和hsa-miR-4792）和三个mRNA（GSR、RAB 3D和EDARADD）的存活相关的ceRNA网络。然后，两个候选德克斯通过实时PCR进行验证。我们的研究构建了一个ceRNA网络，为ALN转移的分子机制和TNBC的潜在治疗靶点提供了新的见解。
The metastatic mechanisms of axillary lymph nodes (ALNs) in triple-negative breast cancer (TNBC) remain unclear. We aimed to identify the potential circRNA regulatory network in ALN metastasis. We performed whole transcriptome sequencing (WTS) to determine the expression profiles of RNAs and screen out differentially expressed messenger RNAs (DEMs), microRNAs (DEMis), and circRNAs (DECs) between ALN-positive and ALN-negative TNBC patients. Functional enrichment analysis and Kaplan–Meier survival analysis were utilized to unearth the potential regulatory mechanisms of the DEMs. A competing endogenous RNA (ceRNA) network was constructed using computational biology. The expression levels of DECs in cell lines were confirmed by real-time polymerase chain reaction (RT‒PCR). Following WTS and differential expression analysis, 739 DEMs, 110 DEMis, and 206 DECs were identified between ALN-positive and ALN-negative TNBC patients. Functional analysis indicated that the DEMs mainly functioned in carcinogenesis and tumor progression-related pathways. ceRNA networks containing eight circRNAs, six miRNAs, and eighteen mRNAs were developed. In the ceRNA network, two mRNAs (RAB3D and EDARADD) that were significantly associated with better overall survival and one mRNA (GSR) that predicted favorable recurrence-free survival in TNBC patients were chosen for further analysis. Then, a survival-related ceRNA network containing two DECs (hsa_circ_0061260 and hsa_circ_0060876), two DEMis (hsa-miR-5000-3p and hsa-miR-4792), and three mRNAs (GSR, RAB3D, and EDARADD) was identified. Then, two candidate DECs were validated by real-time PCR. Our research constructed a ceRNA network that provides novel insights into the molecular mechanism of ALN metastasis and potential therapeutic targets in TNBC.
登录
查看更多内容
影响因子：
3.3
作者：
Zhai X;Wu Y;Wang Z;Zhao D;Li H;Chong T;Zhao J
通讯作者：
Zhao J
影响因子：
254.7
作者：
Siegel, Rebecca;Ma, Jiemin;Jemal, Ahmedin
通讯作者：
Jemal, Ahmedin
影响因子：
2.7
作者：
Li, Meng;Bai, Yu-Ting;Meng, Jian
通讯作者：
Meng, Jian
circFBXW7 通过海绵 miR-197-3p 并编码三阴性乳腺癌中的 185 个氨基酸蛋白抑制恶性进展
影响因子：
8.8
作者：
Ye, Feng;Gao, Guanfeng;Tang, Hailin
通讯作者：
Tang, Hailin
影响因子：
45.3
作者：
Liedtke, Cornelia;Mazouni, Chafika;Pusztai, Lajos
通讯作者：
Pusztai, Lajos