Construction and analysis of expression profile of exosomal lncRNAs in pleural effusion in lung adenocarcinoma

Abstract

Background Lung adenocarcinoma (LUAD) is a highly malignant tumor with a very low five‐year survival rate. In this study, we aimed to identify differentially expressed long‐chain non‐coding RNA (lncRNAs) and mRNAs from benign and malignant pleural effusion exosomes. Methods We used gene microassay and quantitative real‐time reverse transcription polymerase chain reaction (RT‐qPCR) to detect and verify differentially expressed mRNAs and lncRNAs in benign and malignant pleural effusion exosomes. Gene Ontology (GO) functional significance and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway significance enrichment analyses were performed to identify the difference in biological processes and functions between different mRNAs. We selected the lncRNA ZBED5‐AS1 with an upregulated differential fold of 3.003 and conducted a preliminary study on its cellular function. Results Gene microassay results revealed that 177 differentially expressed lncRNAs were upregulated, and 215 were downregulated. The top 10 upregulated were FMN1, AL118505.1, LINC00452, AL109811.2, CATG00000040683.1, AC137932.1, AC008619.1, AL450344.1, AC092718.6, and ZBED5‐AS1. The top 10 downregulated were TEX41, G067726, JAZF1‐AS1, AC027328.1, AL445645.1, AL022345.4, AC008572.1, AC123777.1, AC093714.1, and PHKG1. For the mRNAs, 79 were upregulated, and 123 were notably downregulated. GO analysis revealed that the upregulated differential mRNAs were mainly involved in “cellular response to acidic pH” (biological processes), “endoplasmic reticulum part” (cellular components), and “at DNA binding, cyclase activity” (molecular functions). KEGG pathways were found to be related to V. cholerae infection, Parkinson's disease, and cell adhesion molecules. RT‐qPCR showed that ZBED5‐AS1 was highly expressed in LUAD tissues, cells, and benign and malignant pleural fluid exosomes. Overexpression of ZBED5‐AS1 could significantly promote the proliferation, migration, invasion, and colony formation of LUAD cells, and knockdown had the opposite consequence. Conclusion The pleural effusion exosomes from patients with LUAD include several improperly expressed genes, and lncRNA‐ZBED5‐AS1 is a new biomarker that aids in our understanding of the occurrence and progression of LUAD.

Long Noncoding RNA ZBED5-AS1 Facilitates Tumor Progression and Metastasis in Lung Adenocarcinoma via ZNF146/ATR/Chk1 Axis

“…ZBED5-AS1 was found to promote the proliferation, migration, and invasion of LUAD cells and inhibit their apoptosis. This outcome is in line with our previous finding that ZBED5-AS1 exerts oncogenic effects on LUAD progression [ 9 ]. Additionally, EMT has been widely acknowledged as a crucial mechanism in the development of tumors.…”

“…Our research group has previously reported that ZBED5-AS1 is differentially expressed in exosomes of pleural effusion of LUAD patients and healthy controls. Additionally, we found that ZBED5-AS1 plays an active role in promoting the proliferation, migration, invasion, and colony formation of LUAD cells [ 9 ]. However, the molecular mechanisms underlying LUAD development and its association with lncRNA ZBED5-AS1 remain unclear.…”

Non-coding RNAs in lung cancer: molecular mechanisms and clinical applications

“…Furthermore, by comparing the plasma of LUAD patients with benign pulmonary nodule patients, Tong et al confirmed 1762 differentially expressed lncRNAs in LUAD patients, 946 in lung squamous cell carcinoma patients, and 298 in SCLC patients (72). Huang et al revealed 177 highly expressed lncRNAs and 215 low expression lncRNAs in the exosomes of LUAD pleural effusion compared with that of benign pleural effusion (73). In addition, Cai et al performed highthroughput sequencing and identified 598 differentially expressed circRNAs between LUAD patients with bone metastasis and patients without bone metastasis, among which 238 were upregulated and 360 were downregulated (74).…”