FOXF1 Adjacent Non-coding Developmental Regulatory RNA Research Articles

Long non-coding RNA FENDRR suppresses cancer-associated fibroblasts and serves as a prognostic indicator in colorectal cancer

Genetically abnormal fibroblasts are notably more prevalent in colorectal cancer (CRC) than in adjacent normal tissue, emphasizing their significance in driving the heterogeneity of the tumor microenvironment. Functioning as a significant regulatory gene in the context of fibrosis, FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) has exhibited abnormal expression in colorectal cancer and interstitial localization in our experiments. However, current research on the role of FENDRR in cancer has focused solely on its impact on cancer cells. Its crucial role in the tumor stroma is yet to be explored. The goal of this study was to understand the relationship between atypical FENDRR expression, its distinct localization, and genetically abnormal fibroblasts in CRC. We aimed to establish the function of FENDRR within the stromal compartment of patients through bioinformatics. Our study confirmed that FENDRR suppresses cancer-associated fibroblasts by inhibiting their activation and collagen generation in CRC. Furthermore, our findings suggest that low FENDRR expression indicates a poor prognosis. Therefore, we propose that FENDRR is a promising therapeutic target for future studies in CRC.

LncRNA FENDRR in Carcinoma-Associated Fibroblasts Regulates the Angiogenesis of Oral Squamous Cell Carcinoma Through the PI3K/AKT Pathway.

Angiogenesis is essential for the development of tumors. Studies have shown that carcinoma-associated fibroblasts (CAFs) are involved in regulating tumor angiogenesis, but the mechanism remains unclear. Recently, long noncoding RNAs (lncRNAs) have been proved to play an important role in the angiogenesis of various tumors. However, there is currently no research involving the regulation of CAFs on the angiogenesis of oral squamous cell carcinoma (OSCC) mediated by lncRNAs. By analyzing microarray data, we identified that the expression of lncRNA FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) in OSCC patients is downregulated, compared to that in normal tissues. Quantitative polymerase chain reaction (qPCR) results demonstrated that FENDRR expression is lower in CAFs compared to normal fibroblasts (NFs) of OSCC patients. KEGG pathway analysis revealed that some genes differentially expressed between CAFs and NFs of HNSCC patients are enriched to the PI3K/AKT pathway. Further experiments confirmed that the downregulation of FENDRR can activate the PI3K/AKT pathway in NFs and enhances the expression of matrix metalloproteinase 9 (MMP9). The overexpression of FENDRR had the opposite effect. Besides, we co-cultured human umbilical vein endothelial cells (HUVECs) with CAFs, and the tube-forming ability of HUVECs co-cultured with CAFs overexpressing FENDRR decreased significantly. However, activation of the AKT pathway of CAFs overexpressing FENDRR can weaken the inhibitory effect of FENDRR on angiogenesis. In summary, our experiments are focused on the influence of lncRNAs in CAFs on OSCC angiogenesis for the first time and prove that FENDRR mediates CAFs’ regulation of OSCC angiogenesis through the PI3K/AKT pathway.

ABHD4-Regulating RNA Panel: Novel Biomarkers in Acute Coronary Syndrome Diagnosis

Background: Acute coronary syndrome (ACS) is a major cause of death all over the world. STEMI represents a type of myocardial infarction with acute ST elevation. We aimed to assess the predictive power of potential RNA panel expression in acute coronary syndrome. Method: We used in silico data analysis to retrieve RNAs related to glycerophospholipid metabolism dysregulation and specific to ACS that results in the selection of Alpha/Beta hydrolase fold domain4 (ABHD4) mRNA and its epigenetic regulators (Foxf1 adjacent noncoding developmental regulatory RNA (FENDRR) lncRNA, miRNA-221, and miRNA-197). We assessed the expression of the serum RNA panel in 68 patients with ACS, 21 patients with chest pain due to non-cardiac causes, and 21 healthy volunteers by quantitative real-time polymerase chain reaction. Results: The study data showed significant down regulation in the expression of the serum levels of FENDRR lncRNA and miRNA-221-3p by 120-fold and 22-fold in Unstable angina (UA) in comparison with healthy volunteers, and by 8.6-fold and 2-fold in ST segment elevation myocardial infarction (STEMI) patients versus UA; concomitant upregulation in the expression of ABHD4 mRNA and miRNA-197-5p by 444-fold and 10-fold in UA compared with healthy volunteers, and by 1.54-fold and 4.5-fold in STEMI versus unstable angina. Performance characteristics analysis showed that the ABHD4-regulating RNA panel were potential biomarkers for prediction of ACS. Moreover, there was a significant association between the 2 miRNAs and ABHD4 mRNA and the regulating FENDRR lncRNA. Conclusion: Collectively, ABHD4 mRNA regulating RNA panel based on putative interactions seems to be novel non-invasive biomarkers that could detect ACS early and stratify severity of the condition that could improve health outcome.

The effect of splicing MST1R in gastric cancer was enhanced by lncRNA FENDRR.

Gastric cancer (GC) poses a serious threat to human health worldwide. Serine/arginine rich splicing factor 1 (SRSF1) has been reported to serve regulatory roles during the tumorigenesis of GC. In addition, the macrophage stimulating 1 receptor (MST1R) signaling pathway was found to participate in the progression of GC. However, the association between MST1R and SRSF1 in the tumorigenesis of GC remains unclear. The expression levels of MST1R and the recepteur d'origine nantais (RON) Δ160 splicing variant were analyzed in cells using western blotting and immunofluorescence staining. Co-immunoprecipitation assays were used to investigate the interaction between SRSF1 and MST1R. A Cell Counting Kit-8 assay was performed to analyze cell viability. Flow cytometry and Transwell assays were used to determine cell apoptosis and invasiveness levels. The potential interaction between SFSR1 and long non-coding RNAs (lncRNAs) was investigated with an online bioinformatics tool. The findings of the present study revealed that the expression levels of MST1R and RON Δ160 were significantly upregulated in GC Kato III cells. SRSF1 was found to be regulated by the lncRNA FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR). The knockdown of SRSF1 or FENDRR downregulated the expression levels of MST1R in Kato III cells. In addition, the expression levels of RON Δ160 were markedly downregulated in Kato III cells following the knockdown of FENDRR. Meanwhile, SRSF1 directly bound to MST1R, while this phenomenon was partially reversed by FENDRR short interfering RNA. FENDRR could interact with SRSF1 in Kato III cells and the knockdown of FENDRR also induced the apoptosis of GC cells. In conclusion, the findings of the present study suggested that the lncRNA FENDRR may function as an oncogene during the progression of GC by regulating alternative splicing of MST1R and SRSF1 expression levels. lncRNA FENDRR may serve as a potential marker for the diagnosis or target for the treatment of GC.

Long Non-coding RNA FENDRR Modulates Autophagy Through Epigenetic Suppression of ATG7 via Binding PRC2 in Acute Pancreatitis.

Acute pancreatitis (AP) is an inflammatory, complicated pancreatic disease, carrying significant morbidity and mortality. However, the molecular and cellular mechanisms involved in AP pathogenesis remain to be elucidated. Here, we explore the role of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) in AP progression. Caerulein with or without LPS- induced or taurolithocholic acid 3-sulfate (TLC-S)-induced AP mouse models and cell models were performed for the validation of FENDRR expression in vivo and in vitro, respectively. Histopathological examinations of pancreatic tissues were performed to evaluate the severity of AP. Transmission electron microscopy was utilized to visualize the autophagic vacuoles. siRNA specifically targeting FENDRR was further applied. Flow cytometry was employed to assess cell apoptosis. ELISA, immunoflureoscence, and western blotting analysis were also performed to determine the levels of inflammatory cytokines and autophagy activity. RNA immunoprecipitation (RIP) and chromatin immunoprecipitation (ChIP) assays were carried out to reveal the epigenetic regulation of FENDRR on ATG7. Additionally, silencing FENDRR was also verified in AP mouse models. Higher FENDRR and impaired autophagy were displayed in both AP mouse models and cell models. FENDRR knockdown dramatically attenuated caerulein- or TLC-S-induced AR42J cells apoptosis and autophagy suppression. Further mechanistic experiments implied that the action of FENDRR is moderately attributable to its repression of ATG7 via direct interaction with the epigenetic repressor PRC2. Moreover, the silencing of FENDRR significantly induced the promotion of ATG7, thus alleviating the development of AP in vivo. Our study highlights FENDRR as a novel target that may contribute to AP progression, suggesting a therapeutic target for AP treatment.

Circulating Coding and Long Non-Coding RNAs as Potential Biomarkers of Idiopathic Pulmonary Fibrosis.

Background: Idiopathic Pulmonary Fibrosis (IPF) is a chronic degenerative disease with a median survival of 2–5 years after diagnosis. Therefore, IPF patient identification represents an important and challenging clinical issue. Current research is still searching for novel reliable non-invasive biomarkers. Therefore, we explored the potential use of long non-coding RNAs (lncRNAs) and mRNAs as biomarkers for IPF. Methods: We first performed a whole transcriptome analysis using microarray (n = 14: 7 Control, 7 IPF), followed by the validation of selected transcripts through qPCRs in an independent cohort of 95 subjects (n = 95: 45 Control, 50 IPF). Diagnostic performance and transcript correlation with functional/clinical data were also analyzed. Results: 1059 differentially expressed transcripts were identified. We confirmed the downregulation of FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) lncRNA, hsa_circ_0001924 circularRNA, utrophin (UTRN) and Y-box binding protein 3 (YBX3) mRNAs. The two analyzed non-coding RNAs correlated with Forced Vital Capacity (FVC)% and Diffusing Capacity of the Lung for carbon monoxide (DLCO)% functional data, while coding RNAs correlated with smock exposure. All analyzed transcripts showed excellent performance in IPF identification with Area Under the Curve values above 0.87; the most outstanding one was YBX3: AUROC 0.944, CI 95% = 0.895–0.992, sensitivity = 90%, specificity = 88.9%, p-value = 1.02 × 10−13. Conclusions: This study has identified specific transcript signatures in IPF suggesting that validated transcripts and microarray data could be useful for the potential future identification of RNA molecules as non-invasive biomarkers for IPF.

LncRNA FENDRR-mediated tumor suppression and tumor-immune microenvironment changes in non-small cell lung cancer.

BackgroundLong noncoding RNAs (lncRNAs) play a key role in the development and progression of many cancer types, including lung cancer. The objective of this study is to examine the function and molecular mechanism of lncRNAs involved in non-small cell lung cancer (NSCLC).MethodsFirst, 7 lung cancer-related differentially expressed LncRNAs were screened from 2 genomic profiling datasets. Of these lncRNAs, FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) was found to be the only one that was both significantly down-regulated in the patients with advanced pathology and negatively correlated with prognosis. Thus, lncRNA FENDRR was further studied in this project. Clinical correlation analysis was further conducted in the GSE30219 dataset and 73 paired lung cancer and noncancerous tissues stored in our lab; Subsequently, we evaluated FENDRR coding potential with the Phylogenetic Codon Substitution Frequencies (PhyloCSF), Coding-Potential Assessment Tool (CPAT), and Coding Potential Calculator (CPC) online analytical tool. The cell growth ability was measured by CCK8 assay and clonogenicity assay, the metastatic capacities were evaluated using Transwell migration and invasion assays. Mechanistically, we analyzed the correlation of FENDRR function in NSCLC with immune response by utilizing The Cancer Genome Atlas (TCGA) data.ResultsResults indicated a negative clinical correlation of FENDRR. Coding potential analysis showed FENDRR as a noncoding RNA. Elevated expression of FENDRR led to cell growth arrest, inhibition of proliferative ability, declined migration and invasion potential of NSCLC cells in vitro. Mechanistically, we discovered that FENDRR expression might be involved in aberrant immune response regulation.ConclusionsTaken together, our results provide a greater understanding of lncRNA FENDRR as a tumor suppressor with respect to tumor-immune interactions in NSCLC.

LncRNA FENDRR Upregulation Promotes Hepatic Carcinoma Cells Apoptosis by Targeting miR-362-5p Via NPR3 and p38-MAPK Pathway.

Background: Abnormal long noncoding RNA FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) expression has been discovered in multiple human cancers pathogenesis, but its role in hepatocellular carcinoma (HCC) cells is rarely reported. Its effects on HCC cells are covered in this study. Materials and Methods: MiR-362-5p and NPR3 expressions in HCC tissues and cell were detected by quantitative real-time polymerase chain reaction and Western blot as needed. Cell viability and apoptosis were detected by MTT assay and flow cytometry, respectively. Target gene and potential binding sites of FENDRR, miR-362-5p, and NPR3 were predicted and confirmed by TargetScan and Starbase, and dual-luciferase reporter assay. Results: FENDRR expression was downregulated while miR-362-5p expression was upregulated in HCC tissues and cells. FENDRR upregulation inhibited HCC cells viability yet induced apoptosis, which was reversed by miR-362-5p. In addition, miR-362-5p resulted in p38-mitogen-activated protein kinase (MAPK) pathway activation and NPR3 expression decrease in HCC cells, which was reversed by FENDRR. Conclusion: FENDRR inhibited HCC cells viability yet promoted apoptosis by targeting miR-362-5p by promoting NPR3 and deactivating p38-MAPK pathway, thus exerting its anticarcinogenic effects in HCC cells.

LncRNA FENDRR suppresses the progression of NSCLC via regulating miR-761/TIMP2 axis

To explore the roles of long noncoding RNA (lncRNA) FOXF1 Adjacent Non-Coding Developmental Regulatory RNA (FENDRR) in human non-small cell lung cancer (NSCLC). The levels of FENDRR in NSCLC cells and tissues were analyzed using qRT-PCR assay. The growth and colony formation abilities of NSCLC cell were analyzed by the MTT and colony formation tests. The mobility and invasiveness of NSCLC cell were analyzed using the wound closure and Transwell invasion assay. The impact of FENDRR on the tumor growth of NSCLC cells in vivo was detected using xenograft model. Bioinformatics analysis and luciferase reporter gene bioassay were selected to identify the bindings sites between miR-761 and FENDRR. Additional, the results of Transwell invasion and colony formation experiments indicated that FENDRR inhibited the aggressiveness of NSCLC depend on miR-761. Tissue inhibitor of metalloproteinase 2 (TIMP2) was identified as the downstream target of miR-761 and its level was positively regulated by FENDRR. Cotransfection assays using A549 and H1975 cells future implied that downexpression of TIMP2 rescued the aggressiveness phenotypes of NSCLC cell inhibited by FENDRR. Altogether, we demonstrated that lncRNA FENDRR suppressed the progression of NSCLC via binding to miR-761 and regulating TIMP2 expression.

LncRNA FENDRR attenuates colon cancer progression by repression of SOX4 protein.

Background and purpose: Homo sapiens FOXF1 adjacent noncoding developmental regulatory RNA (FENDRR) is a novel long noncoding RNA (lncRNA) exerting important effects on transcriptional and post-transcriptional regulation. The purpose of this study was to investigate the potential role of FENDRR in colon cancer.Methods: Multiple cellular and molecular biology experiments were performed in the present study, such as CCK-8, Western blot, immunohistochemistry, confocal immunofluorescent and animal studies.Results: We determined that attenuation of FENDRR was a frequent event in colon cancer tissues and colon cancer cell lines, in contrast to their normal counterparts. Low levels of FENDRR were associated with the clinical stages and poor prognosis. Moreover, ectopic expression of FENDRR repressed colon cancer cell viability, invasion and epithelial–mesenchymal transition. Furthermore, through a series of in vitro and in vivo assays, we reported the discovery of FENDRR modulating the expression of SOX4 protein, and hence in the progression of colon cancer.Conclusion: Based on these data, we demonstrated that FENDRR may function as a tumor-suppressor gene by repressing SOX4 and as a potential therapeutic target for colon cancer.

Long non-coding RNA FOXF1 adjacent non-coding developmental regulatory RNA inhibits growth and chemotherapy resistance in non-small cell lung cancer.

IntroductionLung cancer is one of the most common malignant neoplasms around the globe. Its most common type is non-small cell lung cancer (NSCLC). The FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) gene is an lncRNA which has been reported to show low expression and a tumor suppressor role in NSCLC.Material and methodsThe expression of FENDRR in NSCLC patients’ tissues and cell line was detected by quantitative real-time PCR. MTT assay was used to detect cell proliferation and chemotherapy resistance. Cell apoptosis was measured by flow cytometry.ResultsThe expression of FENDRR was low in NSCLC tissues and cells in contrast to control tissues and cells, and low FENDRR expression correlated with high TNM stages and poor differentiation of NSCLC, and could be a promising prognostic factor for NSCLC. FENDRR enhancement could inhibit the proliferation ability and advance cell apoptosis of A549 cells. The expression of FENDRR in NSCLC tissues and cells insensitive to cisplatin was much lower than that in NSCLC tissues and cells sensitive to cisplatin. The chemotherapy resistance to cisplatin of A549/DDP cells was depressed by FENDRR enhancement, and IC50 for cisplatin presented a conspicuous depression. FENDRR up-regulation inhibited cell viability of A549/DDP cells under treatment with 5 µg/ml DDP. TCGA Pan-Cancer (PANCAN) showed that the expression of FENDRR was negatively correlated with the expression of ABCC10 in lung cancer, and our western blot found that FENDRR up-regulation inhibited the expression of ABCC10 in A549/DDP cells.ConclusionsLncRNA FENDRR has low expression in NSCLC and functions as a potential tumor-suppressing gene to inhibit growth and chemotherapy resistance of NSCLC cells.

Long non-coding RNA FENDRR inhibits NSCLC cell growth and aggressiveness by sponging miR-761.

The aim of this paper is to investigate the functions of long noncoding RNA (lncRNA) FOXF1 Adjacent Non-Coding Developmental Regulatory RNA (FENDRR) in the growth and aggressiveness of non-small cell lung cancer (NSCLC). The expression of FENDRR in NSCLC tissues and cell lines was detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and colony formation assays were conducted to explore the roles of FENDRR on the growth of NSCLC cell. The wound healing and transwell invasion assays were conducted to explore the impact of FENDRR on NSCLC cell migration and invasion. The apoptosis of NSCLC cell was detected using flow cytometer-based Annexin V/Propidium Iodide (PI) dual staining. The xenograft model was conducted to investigate the effect of FENDRR on the growth of NSCLC cell in vivo. The expression of Ki67 was measured by immunohistochemical (IHC) staining using Ki67 antibody. Bioinformatics analysis and Luciferase reporter assay were applied to identify that miR-761 was the target of FENDRR. Additional, colony formation and transwell experiments were utilized to confirm that FENDRR inhibited the growth and aggressiveness of NSCLC cell by regulating miR-761. We found a marked down-regulation of FENDRR in NSCLC tissues compared to tumor-adjacent tissues. FENDRR down-expression was detected in four NSCLC cell lines (H1650, HCC827, H1975 and A549) compared to the human non-tumorigenic bronchial epithelial cell, BEAS-2B. Low expression of FENDRR was identified as a predictive factor for poor prognosis of patients with NSCLC. The over-regulation of FENDRR inhibited the proliferation, migration and invasion capacities of NSCLC cell and promoted the apoptosis of NSCLC cell in vitro whereas the down-regulation of FENDRR caused the opposite results. Moreover, the over-expression of FENDRR restrained the growth of NSCLC cell in vivo. We found that there were potential binding sites between FENDRR and miR-761 and the level of miR-761 was inversely associated with the expression of ENDRR in NSCLC tissues. Finally, the rescue experiments suggested that the anti-oncogenic role of FENDRR was at least partially mediated by miR-761 in NSCLC. We found that FENDRR was down-expressed in NSCLC and the over-expression of FENDRR inhibited the malignant phenotypes of NSCLC cell by binding to miR-761 competitively.

Downregulation of long noncoding RNA FENDRR predicts poor prognosis in renal cell carcinoma.

Long noncoding RNA FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) dysregulation associates with multiple types of human cancer. However, the biological functions of FENDRR in renal cell carcinoma are unresolved. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was performed to determine the expression level of FENDRR in renal cell carcinoma tissues. An RNA interference assay and ectopic expression experiments were conducted to evaluate the effects of FENDRR on cell proliferation, migration, invasion and colony formation in vitro. RNA immunoprecipitation was conducted to identify proteins associated with FENDRR. It was observed that FENDRR is frequently downregulated in renal cell carcinoma and overexpression of FENDRR attenuated proliferation, migration, invasion and colony growth of renal carcinoma cells. Conversely, knockdown of FENDRR promotes proliferation and invasiveness of renal carcinoma cells. Downregulation of FENDRR associates with poor prognosis of renal cell carcinoma. Mechanistically, it was identified that FENDRR may bind to Polycomb Repressive Complex 2 and lysin methyltransferase 2A histone modifying complexes. In summary, FENDRR acts as an tumor suppressor in renal cell carcinoma and may serve as a candidate target for gene therapy.

Screening for key lncRNAs in the progression of gallbladder cancer using bioinformatics analyses.

The present study aimed to investigate key long non-coding RNAs (lncRNAs) and genes, and to obtain insights into their roles in the progression of gallbladder cancer (GBC). The gene expression profile and non-coding RNA profile of GSE62335, which included five separate GBC tissue samples and five matched adjacent gallbladder normal tissue samples, was downloaded from the Gene Expression Omnibus database. The differentially expressed lncRNAs and mRNAs in the GBC tissues were identified, following which RNA binding protein analysis was performed using starBase v2.0 and the co-expressed lncRNA-mRNA pairs were predicted. Gene Ontology enrichment analysis for mRNAs was performed using the Database for Annotation Visualization and Integrated Discovery online tool. In addition, upstream microRNAs (miRNAs) were predicted for the co-expressed lncRNAs and mRNAs. The results revealed that a total of 89 upregulated (13 lncRNAs and 76 mRNAs) and 261 downregulated transcripts (27 lncRNAs and 234 mRNAs) were identified in the GBC tissues. Only 9 lncRNAs had co-expressed mRNAs, and lncRNA forkhead box P2 (FOXP2) was co-expressed with the highest number of mRNAs, which were significant associated with the function of cell adhesion. In addition, the analysis of upstream miRNAs showed that FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) had common upstream miRNAs, including miR-18b-5p, with another 119 differentially expressed genes, and that FENDRR was co-expressed with adenomatosis polyposis coli downregulated 1 (APCDD1) and v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT). Taken together, the results suggested that the lncRNAs FOXP2 and FENDRR may be crucial in promoting the progression of GBC via cell adhesion and regulating miR-18b-5p, or through interactions with KIT and APCDD1, respectively.

A functional CNVR_3425.1 damping lincRNA FENDRR increases lifetime risk of lung cancer and COPD in Chinese.

Genomic imbalance referring to somatic variation in chromosome copies represents the most frequent event in tumorigenesis. Germline copy number variations (gCNVs) overlapping regions of genomic imbalance harbor similar structural characteristics and thus influence tumor susceptibility. We aimed to test effects of such gCNVs on the risk of lung cancer and chronic obstructive pulmonary disease (COPD). Genomic imbalance of lung cancer was determined by the array comparative genomic hybridization (aCGH), and common gCNVs at these imbalance regions were genotyped in lung cancer-based and COPD-based retrospective studies. Functional assays were conducted to assess function of promising CNVs. A total of 115 genomic imbalances were discovered occurring at a frequency of more than 25%. The CNVR_3425.1, overlapping the chr16q24.1 with genomic imbalance, was significantly associated with increased risks of lung cancer (OR = 1.76; 95% CI = 1.46-2.11) and COPD (OR = 1.98; 95% CI = 1.57-2.51). The increase copy of CNVR_3425.1 forms a new additional truncated FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) sequences comparing the gene promoter and perturbs the transcriptional factors (TFs) binding to the original FENDRR promoter and further downregulates FENDRR, a long intergenic non-coding RNA (lincRNA) that functions to inhibit lung cancer by affecting expressions of an abundant number of genes, including the tumor suppressor FOXF1. FENDRR can upregulate FOXF1 by competitively binding to miR-424. The TFs early growth response 1 (EGR1) and transcription factor AP-2 alpha (TFAP2A) were further found to involve the CNVR_3425.1-mediated FENDRR dysregulation. These findings suggested the CNVR_3425.1 to be a possibly predictive biomarker for the risk of lung cancer and COPD, and targeted molecular therapy pertaining to FENDRR upregulation may be a valuable pathway to fight two diseases.