Identification of Key lncRNA–mRNA Pairs and Functional lncRNAs in Breast Cancer by Integrative Analysis of TCGA Data

Abstract

Long non-coding RNAs (lncRNAs) play an important role in many diseases and are involved in the post-transcriptional regulatory network of tumors. The purpose of this study is to mine new lncRNA–mRNA regulatory pairs and analyze the new mechanism of lncRNA involvement in breast cancer progression. Using breast cancer miRNA and mRNA expression profiling from The Cancer Genome Atlas (TCGA), we identified 59 differentially expressed lncRNAs, 88 differentially expressed miRNAs, and 1,465 differentially expressed mRNAs between breast cancer tissue and adjacent normal breast cancer. Whereafter, four candidate lncRNAs (FGF14-AS2, LINC01235, AC055854.1, and AC124798.1) were identified by the Kaplan–Meier (K–M) plotter. Furthermore, we screened the hub lncRNA (LINC01235) through univariate Cox analysis, multivariate Cox analysis, and qPCR validation, which was significantly correlated with breast cancer stage, ER status, and pathological N. Subsequently, 107 LINC01235-related mRNAs were obtained by combining differentially expressed miRNAs, differentially expressed mRNAs, and LINC01235 targeting miRNAs and mRNAs. The protein–protein interaction (PPI) network was established by Cytoscape software, and 53 key genes were screened. Function and pathway enrichment showed that LINC01235-related key genes might be involved in the process of cell differentiation, cell proliferation, and p53 signal pathway. In addition, LINC01235 has been confirmed to regulate the proliferation, migration, and invasion of MCF-7 cells in in vitro experiments. Furthermore, we screened three mRNAs (ESR1, ADRA2A, and DTL) associated with breast cancer drug resistance from key genes. Through RNA interference experiments in vitro and correlation analysis, we found that there was a negative feedback mechanism between LINC01235 and ESR1/ADRA2A. In conclusion, our results suggest that LINC01235-ESR1 and LINC01235-ADRA2A could serve as important co-expression pairs in the progression of breast cancer, and LINC01235 plays a key role as an independent prognostic factor in patients with breast cancer. The findings of this work greatly increase our understanding of the molecular regulatory mechanisms of lncRNA in breast cancer.

Use of miRNA Sequencing to Reveal Hub miRNAs and the Effect of miR-582-3p/SMAD2 in the Progression of Hepatocellular Carcinoma

“…This may be because the expression pattern of miR-378i itself in hepatocellular carcinoma is not correlated with survival data, only the low expression of miR-378i is correlated with tumorigenesis, while the high expression of miR-378i is correlated with tumor progression. Similar studies have been reported in the past, such as bidirectional regulation of LINC01235 in breast cancer, and different expression patterns of DAPLE gene in different stages of colon cancer ( Li et al, 2021 ; Aznar et al,2015 ). It may also be related to the immune escape mechanism of hepatocellular carcinoma cells.…”

Detection and analysis of long noncoding RNA expression profiles related to epithelial–mesenchymal transition in keloids

“…As an emerging class of regulatory RNAs, lncRNAs may participate in fundamental processes including cell cycle regulation, proliferation, apoptosis, self-renewal, metastasis and the DNA damage response through transcriptional or posttranscriptional regulation and thus give rise to diseases. Abnormally expressed lncRNAs play a key role in fibrosis [ 10 ] and different types of cancer, including breast cancer [ 11 – 13 ], lung cancer [ 14 , 15 ], colorectal cancer [ 16 , 17 ], esophageal squamous cell carcinoma [ 18 ], and cutaneous squamous cell carcinoma [ 19 , 20 ].…”

PathExpSurv: Pathway Expansion for Explainable Survival Analysis and Disease Gene Discovery

“…For breast cancer, Wang et al (2015) showed the close relationship between the expression of BAMBI and the proliferation and migration of breast cancer. The high expression of LINC01235 was associated with poor prognosis of breast cancer patients (Li et al, 2021). IFIT2 was considered a tumor suppressor in breast cancer (Zhang et al, 2020), as it had been identified to inhibit cancer cell growth and migration, and promoted cell apoptosis.…”