Clinical Value and Prospective Pathway Signaling of MicroRNA-375 in Lung Adenocarcinoma: A Study Based on the Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Bioinformatics Analysis

Abstract

BackgroundLung adenocarcinoma (LUAD) is the most frequent lung cancer. MicroRNAs (miRNAs) are believed to have fundamental roles in tumorigenesis of LUAD. Although miRNAs are broadly recognized in LUAD, the role of microRNA-375 in LUAD is still not fully elucidated.Material/MethodsWe evaluated the significance of miR-375 expression in LUAD by using analysis of a public dataset from the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) database and a literature review. Furthermore, we investigated the biological function of miR-375 by gene ontology enrichment and target prediction analysis.ResultsMiR-375 expression was significantly higher in LUAD by TCGA data compared to normal lung tissue (p<0.0001). In addition, a common pattern of upregulation for miR-375 in LUAD was found in our review of the literature. A total of 682 genes, both LUAD-related and miR-375-related, were obtained from the analytical integration. Critical pathways were unveiled in the network analysis of the overlaps, such as pentose and glucuronate interconversions, ascorbate and aldarate metabolism, and starch and sucrose metabolism. Furthermore, we identified covert miR-375 associated genes that might participate in LUAD by network analysis, such as FGF2 (fibroblast growth factor 2), PAX6 (paired box 6), and RHOJ. The expression of these three genes were all downregulated in LUAD. Finally, FGF2 was revealed to be negatively correlated with miR-375 in LUAD (r=−0.1821, p=0.0001).ConclusionsOverall, our study provides evidence that miR-375 is essential for the progression of LUAD.

Genetic network and gene set enrichment analyses identify MND1 as potential diagnostic and therapeutic target gene for lung adenocarcinoma

“…In China from 2008 to 2012 lung cancer was the leading cause of cancer-related death 3 , with the crude rates of incidence and deaths of 54.66/100,000 and 45.60/100,000, respectively. Squamous cell carcinoma and small cell lung cancer have been the most prevailing lung malignancy subtypes in the past; however, lung adenocarcinoma (LUAD) has recently emerged as the most common and most aggressive histological type 4 , with most cases being diagnosed at advanced stages. LUAD generally grows in the outer regions of the lungs for a long time before the appearance of symptoms, including mild insufficiency of breath, subtle weight loss, and a general sense of being unwell.…”

Effects of hub genes on the clinicopathological and prognostic features of lung adenocarcinoma

“…Without sufficient early detection methods and effective therapeutic strategies during the early tumor stages, the mortality rate of patients with LUAD has not markedly decreased in recent years (5). Therefore, further insight into the mechanisms responsible for the development and progression of LUAD is urgently required (6).…”

Identification of a Potentially Functional microRNA–mRNA Regulatory Network in Lung Adenocarcinoma Using a Bioinformatics Analysis

“…LUAD is characterized by rapid progression and early development of metastases and a high recurrence rate, with the highest morbidity and mortality in both genders ( Bray et al, 2018 ; Cao and Chen, 2019 ; Siegel et al, 2020 ). The overall 5-year survival rates for LUAD only reach approximately 20% ( Bray et al, 2018 ; Miller et al, 2019 ) given the lack of early detection and limited effective therapies at earlier stages of disease ( Gan et al, 2017 ). LUAD patients have an 80% chance of surviving 5 years if diagnosed at an early stage ( Henschke et al, 2006 ).…”