Bronchopulmonary dysplasia (BPD) manifests in premature neonates with aberrant pulmonary function. Numerous long non-coding RNAs (lncRNAs) have been implicated in the pathogenesis of BPD. This study aims to elucidate the impact of the lncRNA myocardial infarction-associated transcript (MIAT) on the initiation and progression of BPD. Initially, BPD murine models were established through hyperoxia induction in newborn mice. Subsequently, MIAT and GATA binding protein 3 (GATA3) expression levels were assessed, and intravenous administration of short hairpin RNAs (shRNAs) targeting MIAT and GATA3 was performed. Pulmonary histological alterations were examined through histological staining. Levels of inflammatory mediators were quantified using enzyme-linked immunosorbent assay (ELISA) kits. The interaction between MIAT and GATA3 was scrutinized through RNA immunoprecipitation, RNA pull-down, and fluorescence in situ hybridization. The downstream mechanisms of GATA3 were explored using bioinformatics analysis. In summary, lncRNA MIAT exhibited elevated expression in the lung tissues of BPD-afflicted mice. MIAT localized to the nucleus and interacted with GATA3, thereby activating the mitogen-activated protein kinase (MAPK) pathway. Knockdown of MIAT or silencing of GATA3 attenuated the inflammatory response, deactivated the MAPK pathway, and ameliorated BPD symptoms in mice, on the other hand, p-Cresyl sulfate potassium can activate the MAPK signaling pathway and attenuates the effects of si-MIAT or si-GAT3. These improvements were characterized by enhanced alveolar differentiation and reduced glycogen and collagen deposition. In conclusion, lncRNA MIAT plays a pivotal role in activating the MAPK pathway and exacerbating hyperoxia-induced BPD in mice through the binding to GATA3. It's an important discovery for the pathogenesis of BPD and may provide some new treatment for infants diagnosed with BPD.

Smoke exposure is associated with bladder cancer (BC). However, little is known about whether the histologic changes of BC can predict the status of smoke exposure. Given this knowledge gap, the current study investigated the potential association between histology images and smoke exposure status. A total of 483 whole-slide histology images of 285 unique cases of BC were available from multiple centers for BC diagnosis. A deep learning model was developed to predict the smoke exposure status and externally validated on BC cases. The development set consisted of 66 cases from two centers. The external validation consisted of 94 cases from remaining centers for patients who either never smoked cigarettes or were active smokers at the time of diagnosis. The threshold for binary categorization was fixed to the median confidence score (65) of the development set. On external validation, AUC was used to assess the randomness of predicted smoke status; we utilized latent feature presentation to determine common histologic patterns for smoke exposure status and mixed effect logistic regression models determined the parameter independence from BC grade, gender, time to diagnosis, and age at diagnosis. We used 2,000-times bootstrap resampling to estimate the 95% Confidence Interval (CI) on the external validation set. The results showed an AUC of 0.67 (95% CI: 0.58-0.76), indicating non-randomness of model classification, with a specificity of 51.2% and sensitivity of 82.2%. Multivariate analyses revealed that our model provided an independent predictor for smoke exposure status derived from histology images, with an odds ratio of 1.710 (95% CI: 1.148-2.54). Common histologic patterns of BC were found in active or never smokers. In conclusion, deep learning reveals histopathologic features of BC that are predictive of smoke exposure and, therefore, may provide valuable information regarding smoke exposure status.

Chronic obstructive pulmonary disease (COPD) is a widespread inflammatory disease with a high mortality rate. Long noncoding RNAs play important roles in pulmonary diseases and are potential targets for inflammation intervention.

The expression of small nucleolar RNA host gene 6 (SNHG6) in mouse lung epithelial cell line MLE12 with or without cigarette smoke extract (CSE) treatment was first detected using quantitative reverse-transcription PCR. ELISA was used to evaluate the release of inflammatory cytokines (TNF-α, IL-1β, and IL-6). The binding site of miR-182-5p with SNHG6 was predicted by using miRanda, which was verified by double luciferase reporter assay.

Here, we revealed that SNHG6 was upregulated in CS-exposed MLE12 alveolar epithelial cells and lungs from COPD-model mice. SNHG6 silencing weakened CS-induced inflammation in MLE12 cells and mouse lungs. Mechanistic investigations revealed that SNHG6 could upregulate IκBα kinase through sponging the microRNA miR-182-5p, followed by activated NF-κB signaling. The suppressive effects of SNHG6 silencing on CS-induced inflammation were blocked by an miR-182-5p inhibitor.

Overall, our findings suggested that SNHG6 regulates CS-induced inflammation in COPD by activating NF-κB signaling, thereby offering a novel potential target for COPD treatment.

Although chronic inflammation, oxidative stress, airway remodeling, and protease-antiprotease imbalance have been implicated in chronic obstructive pulmonary disease (COPD), the exact pathogenesis is still obscure. Gene transcription and post-transcriptional regulation have been taken into account as key regulators of COPD occurrence and development. Identifying the hub genes and constructing biological regulatory networks at the post-transcriptional level will help extend current knowledge on COPD pathogenesis and develop potential drugs.

All lung tissues from non-smokers (n = 6), smokers without COPD (smokers, n = 7), and smokers with COPD (COPD, n = 7) were collected to detect messenger RNA (mRNA), microRNA (miRNA), circular RNA (circRNA), and long non-coding RNA (lncRNA) expression and identify the hub genes. Biological regulatory networks were constructed at the post-transcriptional level, including the RNA-binding protein (RBP)-hub gene interaction network and the competitive endogenous RNA (ceRNA) network. In addition, we assessed the composition and abundance of immune cells in COPD lung tissue and predicted potential therapeutic drugs for COPD. Finally, the hub genes were confirmed at both the RNA and protein levels.

Among the 20 participants, a total of 121169 mRNA transcripts, 1871 miRNA transcripts, 4244 circRNA transcripts, and 122130 lncRNA transcripts were detected. There were differences in the expression of 1561 mRNAs, 48 miRNAs, 33 circRNAs, and 545 lncRNAs between smokers and non-smokers, as well as 1289 mRNAs, 69 miRNAs, 32 circRNAs, and 433 lncRNAs between smokers and COPD patients. 18 hub genes were identified in COPD. TGF-β signaling and Wnt/β-catenin signaling may be involved in the development of COPD. Furthermore, the circRNA/lncRNA-miRNA-mRNA ceRNA networks and the RBP-hub gene interaction network were also constructed. Analysis of the immune cell infiltration level revealed that M2 macrophages and activated NK cells were increased in COPD lung tissues. Finally, we identified that the ITK inhibitor and oxybutynin chloride may be effective in treating COPD.

We identified several novel hub genes involved in COPD pathogenesis. TGF-β signaling and Wnt/β-catenin signaling were the most dysregulated pathways in COPD patients. Our study constructed post-transcriptional biological regulatory networks and predicted small-molecule drugs for the treatment of COPD, which enhanced the existing understanding of COPD pathogenesis and suggested an innovative direction for the therapeutic intervention of the disease.

Chronic obstructive pulmonary disease (COPD) is characterized by progressive and irreversible airflow obstruction with abnormal lung function. Because its pathogenesis involves multiple aspects of oxidative stress, immunity and inflammation, apoptosis, airway and lung repair and destruction, the clinical approach to COPD treatment is not further updated. Therefore, it is crucial to discover a new means of COPD diagnosis and treatment. COPD etiology is associated with complex interactions between environmental and genetic determinants. Numerous genes are involved in the pathogenic process of this illness in research samples exposed to hazardous environmental conditions. Among them, Long non-coding RNAs (lncRNAs) have been reported to be involved in the molecular mechanisms of COPD development induced by different environmental exposures and genetic susceptibility encounters, and some potential lncRNA biomarkers have been identified as early diagnostic, disease course determination, and therapeutic targets for COPD. In this review, we summarize the expression profiles of the reported lncRNAs that have been reported in COPD studies related to environmental risk factors such as smoking and air pollution exposure and provided an overview of the roles of those lncRNAs in the pathogenesis of the disease.

Tobacco smoke (TS) is the major cause of lung cancer. The abnormal proliferation and epithelial-mesenchymal transition (EMT) of lung cells promote occurrence and development of lung cancer. The p38 pathway intervenes in this cancer development. Hesperidin also serves a role in human health and disease prevention. The roles of p38 in TS-mediated abnormal cell proliferation and EMT, and the hesperidin intervention thereof are not yet understood. In the present study, it was demonstrated that TS upregulated proliferating cell nuclear antigen, vimentin and N-cadherin expression, whereas it downregulated E-cadherin expression, as assessed using western blotting and reverse transcription-quantitative PCR. Furthermore, it was observed that inhibition of the p38 pathway inhibit TS-induced proliferation and EMT. Hesperidin treatment prevented the TS-induced activation of the p38 pathway, EMT and cell proliferation in mouse lungs. The findings of the present study may provide insights into the pathogenesis of TS-related lung cancer.

LINC00599 has been reported to be upregulated in response to cigarette smoking. However, the effect and underlying mechanism of LINC00599 in chronic obstructive pulmonary disease (COPD) are still under exploration. In this study, LINC00599 was upregulated in the COPD patients and was of clinical value to distinguish COPD patients. COPD cell models were established using 16HBE cells under cigarette smoke extract (CSE) treatment. LINC00599 levels were elevated in a dose and time-dependent way in response to CSE stimulation. The effect of LINC00599 on CSE-induced 16HBE cells was explored. The results showed that LINC00599 deficiency reversed the CSE-induced inhibition on cell viability and proliferation, and rescued the CSE-induced enhancement on cell 16HBE cell apoptosis and inflammation response. Moreover, LINC00599 bound with miR-212-5p to upregulate the BASP1 (brain abundant membrane attached signal protein 1) expression. MiR-212-5p was expressed at a low level in the tissue samples of COPD patients, and its levels were upregulated in LINC00599 silenced cells. BASP1 was targeted by miR-212-5p and its upregulation was identified in the tissue samples of COPD patients and cell models. BASP1 levels were downregulated after miR-212-5p overexpression or LINC00599 silencing. Moreover, the rescue assays demonstrated that BASP1 overexpression reversed the effect of silenced LINC00599 on 16HBE cells after CSE treatment, which indicated that LINC00599 promoted the COPD development by regulating BASP1 expression. In conclusion, LINC00599 facilitated CSE-induced cell apoptosis and inflammation response, while inhibiting the cell viability and proliferation in COPD progression via modulating miR-212-5p/BASP1 axis.