Abstract
Lung adenocarcinoma (LUAD) is the main cause of cancer-related deaths worldwide. Long noncoding RNAs have been reported to play an important role in various cancers due to their special functions. Therefore, identifying the lncRNAs involved in LUAD tumorigenesis and development can help improve therapeutic strategies. The TCGA-LUAD RNA expression profile was downloaded from The Cancer Genome Atlas, and a total of 49 differential lncRNAs, 112 differential miRNAs, and 2,953 differential mRNAs were screened. Through Kaplan–Meier curves, interaction networks, hub RNAs (lncRNAs, miRNAs, and mRNAs) were obtained. These hub genes are mainly involved in cell proliferation, cell cycle, lung development, and tumor-related signaling pathways. Two lncRNAs (SMIM25 and PCAT19) more significantly related to the prognosis of LUAD were screened by univariate Cox analysis, multivariate Cox analysis, and risk model analysis. The qPCR results showed that the expression levels of SMIM25 and PCAT19 were downregulated in clinical tissues, A549 and SPC-A1 cells, which were consistent with the bioinformatics analysis results. Subsequently, the PCAT19/miR-143-3p pairs were screened through the weighted gene co-expression network analysis and miRNA-lncRNA regulatory network. Dual luciferase detection confirmed that miR-143-3p directly targets PCAT19, and qPCR results indicated that the expression of the two is positively correlated. Cell function tests showed that overexpression of PCAT19 could significantly inhibit the proliferation, migration, and invasion of A549 and SPC-A1 cells. In contrast, knockout of PCAT19 can better promote the proliferation and migration of A549 and SPC-A1 cells. The expression of PCAT19 was negatively correlated with tumor grade, histological grade, and tumor mutation load in LUAD. In addition, co-transfection experiments confirmed that the miR-143-3p mimic could partially reverse the effect of PCAT19 knockout on the proliferation of A549 and SPC-A1 cells. In summary, PCAT19 is an independent prognostic factor in patients with LUAD that can regulate the proliferation, migration, and invasion of LUAD cells and may be a potential biomarker for the diagnosis of LUAD. PCAT19/miR-143-3p plays a very important regulatory role in the occurrence and development of LUAD.
Highlights
Lung cancer is one of the most common malignant tumors in the world, of which non–small cell lung cancer (NSCLC) is the main subtype (Gandhi et al, 2018; Ferlay et al, 2019; Cai and Liu, 2021)
The results showed that these Long noncoding RNAs (lncRNAs)-associated mRNAs were obviously associated with cell senescence, cell division, cell cycle, angiogenesis, FIGURE 2 | Venn diagram of the common (A) miRNAs and (B) mRNAs between differentially expressed miRNAs/mRNAs and target miRNAs/mRNAs. (C) Sankey diagram of the competing endogenous RNA (ceRNA) network in lung adenocarcinoma
We found that two lncRNAs (SMIM25 and PCAT19) were more significantly related to the prognosis of patients with lung adenocarcinoma (LUAD) (Figure 4A)
Summary
Lung cancer is one of the most common malignant tumors in the world, of which non–small cell lung cancer (NSCLC) is the main subtype (Gandhi et al, 2018; Ferlay et al, 2019; Cai and Liu, 2021). Lung adenocarcinoma (LUAD) is the most common NSCLC and accounts for a large proportion of cancerrelated deaths worldwide (Liu et al, 2019; Siegel et al, 2019). MicroRNAs (miRNAs) are small endogenous noncoding RNAs that play an important role in regulating gene expression, and their regulatory networks are involved in many biological processes (Ali Syeda et al, 2020). The cross-talk between ceRNAs is achieved by lncRNA-miRNA-mRNA networks. This delicate and complex regulatory network may contribute to a more precise understanding of the disease process (Wang et al, 2019; Zhou et al, 2019; Ma et al, 2020).
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