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Identification of LncRNA CARD8-AS1 as a Potential Prognostic Biomarker Associated With Progression of Lung Adenocarcinoma

ABSTRACT: Introduction: Long non-coding RNAs (lncRNAs) exhibit crucial roles in human tumors. However, the role of lncRNA CARD8-AS1 in lung adenocarcinoma remains elusive. This study investigated the role of CARD8-AS1 in lung adenocarcinoma. Materials and Methods: The expression of CARD8-AS1 was detected by RT-qPCR analysis and confirmed using an online database. The clinical value of CARD8-AS1 was evaluated using the Kaplan-Meier curve and multivariate Cox regression analyses. The effects of CARD8-AS1 on cancer cell proliferation, migration, and invasion potential were assessed through several cellular experiments. Western blot assay was used to measure Bcl-2 and Bax protein levels. The interaction among CARD8-AS1, miR-650, and Bax, was assessed using a dual-luciferase reporter assay. Results: The expression of CARD8-AS1 was decreased in lung adenocarcinoma tissues and cell lines (p < 0.001). Low expression of CARD8-AS1 was related to tumor size (p = 0.042), TNM stage (p = 0.021), lymph node metastasis (p = 0.025), and poor overall survival (p < 0.05). Elevated expression of CARD8-AS1 could suppress cellular viability, migration potential, and invasion ability (p < 0.05). The Bcl-2 protein levels were decreased while Bax levels were increased by overexpression of CARD8-AS1 (p < 0.001). miR-650 may thus be a direct target of CARD8-AS1 and Bax may be a direct target of miR-650. Discussion: CARD8-AS1 expression was downregulated in lung adenocarcinoma and associated with several clinical parameters. CARD8-AS1 exerted tumor-suppressive effects by targeting the miR-650 and then regulating Bax expression. CARD8-AS1/miR-650 may serve as novel prognostic biomarkers and potential therapeutic targets for the treatment of lung adenocarcinoma.

SUBMITTER: Ji Y

PROVIDER: S-EPMC9302548 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundEnhancer RNAs (eRNAs) are demonstrated to be closely associated with tumourigenesis and cancer progression. However, the role of eRNAs in lung adenocarcinoma (LUAD) remains largely unclear. Thus, a comprehensive analysis was constructed to identify the key eRNAs, and to explore the clinical utility of the identified eRNAs in LUAD.MethodsFirst, LUAD expression profile data from the Cancer Genome Atlas (TCGA) dataset and eRNA-relevant information were integrated for Kaplan-Meier survival analysis and Spearman's correlation analysis to filtered the key candidate eRNAs that was associated with survival rate and their target genes in LUAD. Then, the key eRNA was selected for subsequent clinical correlation analysis. KEGG pathway enrichment analyses were undertaken to explore the potential signaling pathways of the key eRNA. Data from the human protein atlas (HPA) database were used to validate the outcomes and the quantitative real time-polymerase chain reaction (qRT-PCR) analysis was conducted to measure eRNA expression levels in tumor tissues and paired normal adjacent tissues from LUAD patients. Finally, the eRNAs were validated in pan-cancer.ResultsAs a result, TBX5-AS1 was identified as the key eRNA, which has T-box transcription factor 5 (TBX5) as its regulatory target. KEGG analysis indicated that TBX5-AS1 may exert a vital role via the PI3K/AKT pathway, Ras signaling pathway, etc. Additionally, the qRT-PCR results and the HPA database indicated that TBX5-AS1 and TBX5 were significantly downregulated in tumour samples compared to matched-adjacent pairs. The pan-cancer validation results showed that TBX5-AS1 was associated with survival in four tumors, namely, adrenocortical carcinoma (ACC), LUAD, lung squamous cell carcinoma (LUSC), and uterine corpus endometrial carcinoma (UCEC). Correlations were found between TBX5-AS1 and its target gene, TBX5, in 26 tumor types.ConclusionCollectively, our results indicated that TBX5-AS1 may be a potential prognostic biomarker for LUAD patients and promote the targeted therapy of LUAD.

Project description:BackgroundLung adenocarcinoma (LUAD) is the leading cause of cancer-related death. This study aimed to develop and validate reliable prognostic biomarkers and signature.MethodsDifferentially expressed genes were identified based on three Gene Expression Omnibus (GEO) datasets. Based on 1052 samples' data from our cohort, GEO and The Cancer Genome Atlas, we explored the relationship of clinicopathological features and NEIL3 expression to determine clinical effect of NEIL3 in LUAD. Western blotting (22 pairs of tumor and normal tissues), Real-time quantitative PCR (19 pairs of tumor and normal tissues), and immunohistochemical analyses (406-tumor tissues subjected to microarray) were conducted. TIMER and ImmuCellAI analyzed relationship between NEIL3 expression and the abundance of tumor-infiltrating immune cells in LUAD. The co-expressed-gene prognostic signature was established based on the Cox regression analysis.ResultsThis study identified 502 common differentially expressed genes and confirmed that NEIL3 was significantly overexpressed in LUAD samples (P < 0.001). Increased NEIL3 expression was related to advanced stage, larger tumor size and poor overall survival (p < 0.001) in three LUAD cohorts. The proportions of natural T regulatory cells and induced T regulatory cells increased in the high NEIL3 group, whereas those of B cells, Th17 cells and dendritic cells decreased. Gene set enrichment analysis indicated that NEIL3 may activate cell cycle progression and P53 signaling pathway, leading to poor outcomes. We identified nine prognosis-associated hub genes among 370 genes co-expressed with NEIL3. A 10-gene prognostic signature including NEIL3 and nine key co-expressed genes was constructed. Higher risk-score was correlated with more advanced stage, larger tumor size and worse outcome (p < 0.05). Finally, the signature was verified in test cohort (GSE50081) with superior diagnostic accuracy.ConclusionsThis study suggested that NEIL3 has the potential to be an immune-related therapeutic target and an independent predictor of LUAD prognosis. We also developed a prognostic signature for LUAD with a precise diagnostic accuracy.

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Identification of LncRNA CARD8-AS1 as a Potential Prognostic Biomarker Associated With Progression of Lung Adenocarcinoma

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