LncRNA HAR1A Suppresses the Development of Non-Small Cell Lung Cancer by Inactivating the STAT3 Pathway

Ma, Jianqun; Cao, Kui; Ling, Xiaodong; Zhang, Ping; Zhu, Jinhong

doi:10.3390/cancers14122845

Cited by 12 publications

(16 citation statements)

References 39 publications

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“…HOTAIR has been reported to be related to the expression of HER2 (encoding human epidermal growth factor receptor 2) and facilitates GC lymph node metastasis [32]. A study using TCGA-based bioinformatics analysis and microarray analysis revealed that HAR1A is a tumor suppressor involved in tumor progression via EMT regulation and is negatively associated with prognosis [33,34]. In our panel, HAR1A also acted as a negative factor for early lymph node metastasis in GC.…”

Section: Discussionmentioning

confidence: 50%

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer

Dong

Xiang

et al. 2023

Preprint

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Background: Lymph node (LN) status is vital to indicate and evaluate the curative potential of relatively early gastric cancer (GC; T1–T2) treatment (endoscopic or surgery). Currently, there is a lack of robust and convenient methods to identify such metastasis before therapeutic decision-making; therefore, there is an urgent need to identify biomarkers that could aid the identification of patients with LN metastasis. Methods: Genome-wide expression profiles of long noncoding RNA (lncRNA) in primary T1 gastric cancer data from The Cancer Genome Atlas (TCGA) was used to identify an lncRNA‑expression signature capable of detecting LN metastasis of GC, and establish a 10-lncRNA risk‑prediction model based on deap learning. The performance of the lncRNA panel in diagnosing LN metastasis was evaluated using both in silico and clinical validation methods. In silico validation was conducted using TCGA and Asian Cancer Research Group (ACRG) datasets. Clinical validation was performed on T1 and T2 patients, and the panel's efficacy was compared with that of traditional tumor markers and computed tomography (CT) scans. Results: Profiling of genome-wide RNA expression identified a panel of lncRNA to predict LN metastasis in T1 stage gastric cancer (area under the curve (AUC) = 0.961). A 10-lncRNA risk-prediction model was then constructed, which was validated successfully in T1 and T2 datasets (TCGA, AUC = 0.852; ACRG, AUC = 0.834). Thereafter, the clinical performance of the lncRNA panel was validated in clinical cohorts (T1, AUC = 0.812; T2, AUC = 0.805; T1+T2, AUC = 0.764). Notably, the 10-lncRNA panel demonstrated significantly better performance compared with CT and conventional tumor markers (carcinoembryonic antigen and carbohydrate antigen 19-9). Conclusions: The novel 10-lncRNA could diagnose LN metastasis robustly in relatively early gastric cancer (T1–T2), with promising clinical potential.

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Section: Discussionmentioning

confidence: 50%

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer

Dong

Xiang

et al. 2023

Preprint

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“…For example, the lncRNAs PLAC2 [29], NUBE2R2-AS1 [30], and OXCT1-AS1 [31], which are upregulated in NSCLC, promote tumor oncogenicity. Conversely, the lncRNAs HAR1A [32], LSAMP-1 [33], and LINC00174 [34] were underexpressed in NSCLC and inhibited cancer aggressiveness. Our literature survey revealed that studies focused on the expression status and detailed roles of POU6F2-AS2 in NSCLC are not extant.…”

Section: Discussionmentioning

confidence: 99%

Long noncoding RNA POU6F2-AS2 contributes to the aggressiveness of nonsmall-cell lung cancer via microRNA-125b-5p-mediated E2F3 upregulation

Huang

Xiao

Tong

2023

Aging

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The role of the majority of long noncoding RNAs (lncRNAs) in the progression of nonsmall-cell lung cancer (NSCLC) remains elusive, despite their potential value, thus warranting in-depth studies. For example, detailed functions of the lncRNA POU6F2 antisense RNA 2 (POU6F2-AS2) in NSCLC are unknown. Herein, we investigated the expression status of POU6F2-AS2 in NSCLC. Furthermore, we systematically delineated the biological roles of POU6F2-AS2 in NSCLC alongside its downstream molecular events. We measured the expression levels of POU6F2-AS2 using quantitative real-time polymerase chain reaction and performed a series of functional experiments to address its regulatory effects in NSCLC cells. Using bioinformatic platforms, RNA immunoprecipitation, luciferase reporter assays, and rescue experiments, we investigated the potential mechanisms of POU6F2-AS2 in NSCLC. Subsequently, we confirmed the remarkable overexpression of POU6F2-AS2 in NSCLC using The Cancer Genome Atlas database and our own cohort. Functionally, inhibiting POU6F2-AS2 decreased NSCLC cell proliferation, colony formation, and motility, whereas POU6F2-AS2 overexpression exhibited contrasting effects. Mechanistically, POU6F2-AS2 acts as an endogenous decoy for microRNA-125b-5p (miR-125b-5p) in NSCLC that causes the overexpression of the E2F transcription factor 3 (E2F3). Moreover, suppressing miR-125b-5p or increasing E2F3 expression levels sufficiently recovered the anticarcinostatic activities in NSCLC induced by POU6F2-AS2 silencing. Thus, POU6F2-AS2 aggravates the oncogenicity of NSCLC by targeting the miR-125b-5p/E2F3 axis. Our findings suggest that POU6F2-AS2 is a novel therapeutic target for NSCLC.

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“…On the other hand, it is important to highlight the function of genes and how they are associated with the development of cancer, which may provide important basic information that could help to improve the screening of candidate biomarkers (57). In particular, information about genes affecting the prognosis of cancer patients could provide insight into the molecular significance of candidate biomarkers for cancer being developed.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive analysis of the significance of METTL7A gene in the prognosis of lung adenocarcinoma

Pan

Xiao

et al. 2022

Front. Oncol.

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BackgroundThe most common subtype of lung cancer, called lung adenocarcinoma (LUAD), is also the largest cause of cancer death in the world. The aim of this study was to determine the importance of the METTL7A gene in the prognosis of patients with LUAD.MethodsThis particular study used a total of four different LUAD datasets, namely TCGA-LUAD, GSE32863, GSE31210 and GSE13213. Using RT-qPCR, we were able to determine METTL7A expression levels in clinical samples. Univariate and multivariate Cox regression analyses were used to identify factors with independent effects on prognosis in patients with LUAD, and nomograms were designed to predict survival in these patients. Using gene set variation analysis (GSVA), we investigated differences in enriched pathways between METTL7A high and low expression groups. Microenvironmental cell population counter (MCP-counter) and single-sample gene set enrichment analysis (ssGSEA) methods were used to study immune infiltration in LUAD samples. Using the ESTIMATE technique, we were able to determine the immune score, stromal score, and estimated score for each LUAD patient. A competing endogenous RNA network, also known as ceRNA, was established with the help of the Cytoscape program.ResultsWe detected that METTL7A was down-regulated in pan-cancer, including LUAD. The survival study indicates that METTL7A was a protective factor in the prognosis of LUAD. The univariate and multivariate Cox regression analyses revealed that METTL7A was a robust independent prognostic indicator in survival prediction. Through the use of GSVA, several immune-related pathways were shown to be enriched in both the high-expression and low-expression groups of METTL7A. Analysis of the tumor microenvironment revealed that the immune microenvironment of the group with low expression was suppressed, which may be connected to the poor prognosis. To explore the ceRNA regulatory mechanism of METTL7A, we finally constructed a regulatory network containing 1 mRNA, 2 miRNAs, and 5 long non-coding RNAs (lncRNAs).ConclusionIn conclusion, we presented METTL7A as a potential and promising prognostic indicator of LUAD. This biomarker has the potential to offer us with a comprehensive perspective of the prediction of prognosis and treatment for LUAD patients.

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LncRNA HAR1A Suppresses the Development of Non-Small Cell Lung Cancer by Inactivating the STAT3 Pathway

Cited by 12 publications

References 39 publications

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer

LncRNA expression signature identified using genome-wide transcriptomic profiling to predict lymph node metastasis in patients with stage T1 and T2 gastric cancer

Long noncoding RNA POU6F2-AS2 contributes to the aggressiveness of nonsmall-cell lung cancer via microRNA-125b-5p-mediated E2F3 upregulation

Comprehensive analysis of the significance of METTL7A gene in the prognosis of lung adenocarcinoma

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