Dataset Information

LncRNA RP11-58O9.2 predicts poor prognosis and promotes progression of non-small cell lung cancer.

ABSTRACT:

Objective

Long non-coding RNAs (lncRNAs) play a crucial role in non-small cell lung cancer (NSCLC). This study aimed to investigate the novel biomarker, lncRNA RP11-58O9.2, in patients with NSCLC.

Methods

RP11-58O9.2 expression in NSCLC cells and tissues was detected by reverse transcription-quantitative polymerase chain reaction. Patient survival was analyzed in relation to RP11-58O9.2 expression levels. RP11-58O9.2 expression was knocked down and endogenous expression was verified in two NSCLC cell lines. Cell proliferation was then assessed by Cell Counting Kit-8 and colony-formation assays, and cell invasion and migration were assessed by Transwell and wound-healing assays, respectively. In vivo experiments were performed in mice, and the combination of RP11-58O9.2 and miR-6749-3p was predicted by miRanda.

Results

RP11-58O9.2 was highly expressed in NSCLC cell lines and tissues, and was associated with advanced stage, lymphatic metastasis, and differentiation group. High RP11-58O9.2 levels were also associated with shorter survival. RP11-58O9.2 knockdown inhibited the proliferation, invasion, and migration of lung cancer cells, and tumor growth in mouse xenografts in vivo. RP11-58O9.2 may target and regulate miR-6749-3p.

Conclusions

LncRNA RP11-58O9.2 is associated with NSCLC prognosis and promotes lung cancer progression. Further studies are needed to investigate the mechanisms and the regulatory association between RP11-58O9.2 and miR-6749-3p.

SUBMITTER: Miao X

PROVIDER: S-EPMC10594974 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

LncRNA RP11-58O9.2 predicts poor prognosis and promotes progression of non-small cell lung cancer.

Miao Xuan X Xi Wen W Bao Yongxia Y

The Journal of international medical research 20231001 10

<h4>Objective</h4>Long non-coding RNAs (lncRNAs) play a crucial role in non-small cell lung cancer (NSCLC). This study aimed to investigate the novel biomarker, lncRNA RP11-58O9.2, in patients with NSCLC.<h4>Methods</h4>RP11-58O9.2 expression in NSCLC cells and tissues was detected by reverse transcription-quantitative polymerase chain reaction. Patient survival was analyzed in relation to RP11-58O9.2 expression levels. RP11-58O9.2 expression was knocked down and endogenous expression was verifi ...[more]

PMID: 37871619

Similar Datasets

Project description:Background: MEOX1 is a homeobox transcriptional factor, and plays essential roles in regulating somite development. Our previous study indicated that MEOX1 is a critical molecular target in mesenchymal-like cancer cells in PTEN-deficient Trastuzumab resistant breast cancer. Despite the potential implication of MEOX1 for the cancer progression, no previous studies examined its level and clinical significance in lung cancer tissues. In this study, we aimed to detect the MEOX1 expression and correlate its level with clinical outcome in non-small-cell lung cancer patients (NSCLC). Methods: MEOX1 gene expression in lung cancer was examined by using the Oncomine database. MEOX1 protein levels were evaluated by IHC using the corresponding primary antibody on two different commercial lung cancer tissue arrays. siRNA knockdown was used to elucidate the function of MEOX1. Results: Analysis of the Oncomine datasets identified that an elevation of MEOX1 in gene amplification in lung cancer tissues in comparison to normal lung tissues. Immunohistochemistical analysis demonstrated that MEOX1 was localized predominantly in the nucleus, and positive rate was 67.3% (111/165) in NSCLC samples. Statistical analysis revealed high levels of MEOX1 significantly correlated with Lymph Node Metastasis and Stage. Kaplan-Meier survival analysis showed that high levels of MEOX1 were significantly associated with unfavorable survival in NSCLC patients, and MEOX1 nucleus staining had worse survival, than did patients with overall expression in lung squamous cell carcinoma patients. Multivariate Cox's regression analysis found that MEOX1 was an independent poor prognostic predictor for patients with NSCLC. Silencing of MEOX1 by specific SiRNA significantly inhibited H460 and H1299 cell proliferation and sphere formation in serum-free medium. Conclusions: Our results firstly indentified that high levels of MEOX1 especially nuclear staining was an independent prognostic factor for NSCLC, and it served a essential roles in the regulation of cell proliferation and colony formation in vitro. It may represent a potential target for the NSCLC treatment.

Project description:BackgroundRecently, increasing evidence has indicated that platelet-activating factor acetylhydrolase 1b catalytic subunit 3 (PAFAH1B3) plays an important role in several cancers. However, its role in lung adenocarcinoma (LUAD) has not been reported until now.MethodsThe expression of PAFAH1B3 in LUAD was determined by using the Gene Expression Profiling Interactive Analysis (GEPIA) database and real-time PCR (RT-PCR), western blot and immunohistochemical (IHC) analyses. A chi-square test was used to investigate the correlation between PAFAH1B3 expression and clinical parameters. Cox regression and Kaplan-Meier analysis were performed to analyze the prognostic value of PAFAH1B3. The CCK-8 assay, clone formation assay, transwell invasion assay and flow cytometry were conducted to detect cell proliferation, clone formation, invasion and the cell cycle. The xenograft tumor model was constructed to explore the function of PAFAH1B3 in vivo. Western blot and IHC analyses were performed to detect epithelial-to-mesenchymal transition (EMT)-related markers. Immune Cell Abundance Identifier (ImmuneCellAI) and IHC analyses were used to analyze the effect of PAFAH1B3 on immune cell infiltration.ResultsOur study showed that the expression of PAFAH1B3 was upregulated in LUAD tissues and cells compared with noncancerous tissues and cells. Additionally, the results indicated that the expression of PAFAH1B3 was positively correlated with distant metastasis, TNM stage and poor clinical outcome and it was an independent prognostic risk factor for LUAD. In addition, silencing PAFAH1B3 suppressed cell proliferation, colony formation, and invasion and increased the cell population in the G0-G1 phases in vitro. Furthermore, our results showed that knockdown of PAFAH1B3 increased the epithelial marker E-cadherin level and decreased the mesenchymal marker N-cadherin level in vitro and in vivo. We also proved that PAFAH1B3 downregulation inhibited tumorigenesis and neutrophil infiltration in the xenograft tumor model.ConclusionOur studies indicate that PAFAH1B3, a prognostic risk factor, promotes proliferation, invasion and EMT and affects immune infiltrates in LUAD.

Project description:Currently, resistance to tyrosine kinase inhibitors, such as erlotinib, has become a major obstacle for improving the clinical outcome of patients with metastatic and advanced‑stage non-small cell lung cancer (NSCLC). While cell behavior can be modulated by long non-coding RNAs (lncRNAs), the roles of lncRNAs within extracellular vesicles (exosomes) are largely unknown. To this end, in this study, the involvement and regulatory functions of potential lncRNAs wrapped by exosomes during the development of chemoresistance in human NSCLC were investigated. Erlotinib-resistant cell lines were established by grafting HCC827 and HCC4006 cells into mice and which were treated with erlotinib. After one treatment course, xenografted NSCLC cells were isolated and transplanted into nude mice again followed by erlotinib treatment. This process was repeated until 4th generation xenografts were isolated and confirmed to be erlotinib-resistant NSCLC cells. lncRNA microarray assays followed by RT‑qPCR were then performed which identified that lncRNA RP11‑838N2.4 was upregulated in erlotinib-resistant cells when compared to normal NSCLC cells. Furthermore, bioinformatics analysis and chromatin immunoprecipitation revealed that forkhead box protein O1 (FOXO1) could bind to the promoter region of lncRNA RP11‑838N2.4, resulting in its silencing through the recruitment of histone deacetylase. Functional experiments demonstrated that the knockdown of lncRNA RP11‑838N2.4 potently promoted erlotinib-induced cytotoxicity. Furthermore, extracellular lncRNA RP11‑838N2.4 could be incorporated into exosomes and transmitted to sensitive cells, thus disseminating erlotinib resistance. Treatment-sensitive cells with exosomes containing lncRNA RP11‑838N2.4 induced erlotinib resistance, while the knockdown of lncRNA RP11‑838N2.4 abrogated this effect. In addition, the serum expression levels of exosomal lncRNA RP11‑838N2.4 were upregulated in patients exhibiting resistance to erlotinib treatment. On the whole, exosomal lncRNA RP11‑838N2.4 may serve as a therapeutic target for patients with NSCLC.

Project description:Backgroundm6 A modification affects the pathological progress of many diseases by affecting RNA stability and translocation. YTHDC2, a m6 A reader, is associated with multiple cancers; however, little is known of its role in non-small cell lung cancer (NSCLC).MethodsThe GEPIA, Oncomine and GEO databases were analyzed to assess expression of YTHDC2 in NSCLC patients. Quantitative polymerase chain reaction, western blot and immunohistochemistry were used to detect YTHDC2 expression in different NSCLC cell lines (H1299, H460, H292 and A549) and patients. The effects of YTHDC2 on NSCLC cell lines (A549 and H1299) proliferation and migration were employed using CCK8 and transwell assays. The potential target RNAs of YTHDC2 were obtained from the POSTAR database. Functional enrichment analysis of YTHDC2 targeted RNAs was performed using the Metascape database.ResultsGEPIA, Oncomine and GEO databases showed low expression of YTHDC2 in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) patients. YTHDC2 expression was significantly decreased in different NSCLC cell lines and our clinical samples. Moreover, low expression of YTHDC2 was significantly associated with poor differentiation, lymph node metastasis, tumor size and stage. In addition, YTHDC2 could suppress the proliferation and migration ability of A549 and H1299 cell lines. Kaplan-Meier Plotter database analysis revealed that patients with low level of YTHDC2 had a significantly poor prognosis. Finally, functional enrichment analysis of YTHDC2 targeted RNAs indicated several enriched pathways related to cancer.ConclusionsThese findings elucidate that YTHDC2 suppresses tumorigenesis in NSCLC, indicating that YTHDC2 may be a promising therapeutic target for NSCLC.Key pointsSIGNIFICANT FINDINGS OF THE STUDY: This study demonstrated that the downregulation of YTHDC2 promotes tumor progression and predicts poor prognosis in non-small cell lung cancer (NSCLC).What this study addsYTHDC2 might be a promising therapeutic target for non-small cell lung cancer (NSCLC).

Dataset Information

LncRNA RP11-58O9.2 predicts poor prognosis and promotes progression of non-small cell lung cancer.

Objective

Methods

Results

Conclusions

Publications

LncRNA RP11-58O9.2 predicts poor prognosis and promotes progression of non-small cell lung cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets