Idiopathic pulmonary fibrosis (IPF), a progressive and fatal lung disease, usually leads to an irreversible distortion of the pulmonary structure. The functional roles of bone marrow‐derived mesenchymal stem cells (BMSC)‐secreted extracellular vesicles (EVs) in fibroblasts have been implicated, yet their actions in the treatment of IPF are not fully understood. This study investigated the roles of BMSC‐derived EVs expressing miR‐29b‐3p in fibroblasts in IPF treatment. EVs derived from BMSCs were successfully isolated and could be internalized by pulmonary fibroblasts, and Cell Counting Kit‐8 (CCK‐8) and Transwell assay results identified that EVs inhibited the activation of fibroblast in IPF. miR‐29b‐3p, frizzled 6 (FZD6), α‐skeletal muscle actin (α‐SMA), and Collagen I expressions were examined, which revealed that miR‐29b‐3p was poorly expressed and FZD6, α‐SMA, and Collagen I were overexpressed in pulmonary tissues. Dual‐luciferase reporter assay results demonstrated that miR‐29b‐3p could inversely target FZD6 expression. The gain‐ and loss‐of‐function assays were conducted to determine regulatory effects of FZD6 and miR‐29b‐3p on IPF. CCK‐8 and Transwell assays results displayed that BMSCs‐derived EVs overexpressing miR‐29b‐3p contributed to inhibited pulmonary interstitial fibroblast proliferation, migration, invasion, and differentiation. Furthermore, the effects of BMSCs‐derived EVs overexpressing miR‐29b‐3p on IPF progression were assessed in vivo, which confirmed the repressive effects of BMSCs‐derived EVs overexpressing miR‐29b‐3p on IPF progression. Collectively, BMSCs‐derived EVs overexpressing miR‐29b‐3p relieve IPF through FZD6.

Chemoresistance is one of the most important biological elements affecting the progression and prognosis of cancer. Long non-coding RNAs (lncRNAs) are important regulators and are aberrantly expressed in various types of cancer in humans, including non-small cell lung cancer (NSCLC). The present study aimed to investigate the effect of lncRNAs on NSCLC resistance to chemotherapy. The relative expression level of epidermal growth factor receptor antisense RNA 1 (EGFR-AS1) was quantified by reverse transcription-quantitative polymerase chain reaction analysis in NSCLC tissues, paired adjacent normal tissues, patient plasma and NSCLC cell lines, and its association with prognosis was assessed by multivariate analysis. The biological functions of EGFR-AS1 in NSCLC cells were determined in vitro. It was found that EGFR-AS1 was abnormally upregulated in NSCLC tissues compared with adjacent normal lung tissues. Furthermore, patients with NSCLC with increased expression of EGFR-AS1 had a poor prognosis. EGFR-AS1 knockdown significantly inhibited NSCLC malignancy in vitro, including cell proliferation and chemoresistance. Furthermore, the expression levels of EGFR-AS1 were increased in plasma samples from patients with cisplatin-based chemotherapy resistance. Bioinformatics analysis and a luciferase reporter assay confirmed that EGFR-AS1 mediated cell proliferation and chemoresistance through directly binding to microRNA-223. Therefore, EGFR-AS1 overexpression-induced chemoresistance can contribute to poor prognosis in NSCLC.Abbreviations: lncRNA, long non-coding RNA; NSCLC, non-small cell lung cancer; EGFR-AS1, epidermal growth factor receptor antisense RNA 1; PRC2, proteasome component 2; LSD1, lysine demethylase 1A; DNMT1, DNA methyltransferase 1; RT-qPCR, reverse transcription-quantitative polymerase chain reaction; ceRNA, competitive endogenous RNA; IGF1R, insulin-like growth factor 1 receptor; PI3K, phosphatidylinositol 3-kinase

Idiopathic pulmonary fibrosis (IPF) is a condition that results in the progressive deterioration of lung function with poor prognosis. The current study is aimed at exploring how microRNA-448 (miR-448) targeting ABCC3 affects fibroblast proliferation, apoptosis, and collagen synthesis of mice with IPF via the Jun N-terminal kinase (JNK) signaling pathway. Bioinformatics and dual-luciferase polymerase chain reaction were used to predict the relationship of miR-448 and ABCC3. The expression of miR-448 and ABCC3 was detected in IPF tissues. Using IPF mouse models, lung fibroblasts for the experiments were treated with miR-448 mimic, miR-448 inhibitor, si-ABCC3, or SP600125 (inhibitor of JNK) to evaluate the cell proliferation and apoptosis in response to miR-448. Reverse transcription quantitative polymerase chain reaction and western blot analysis were used to identify the expression of miR-448, ABCC3, and the activation of the JNK signaling pathway. ABCC3 was targeted and downregulated by miR-448 based on bioinformatics prediction and dual-luciferase reporter gene assay.Additionally, miR-448 was found to be highly expressed in IPF lung tissues with low expression levels of ABCC3. In response to the treatment of miR-448 mimic or si-ABCC3, lung fibroblasts exhibited decreased cell proliferation and increased apoptotic rates, whereas the miR-448 inhibitor reversed the conditions. Notably, we also found that miR-448 mimic inhibited the JNK signaling pathway. In conclusion, by using miR-448 to target and downregulate ABCC3 to block the JNK signaling pathway in mice with IPF, we found an increase in fibroblast apoptosis, inhibited cell proliferation, and decreased collagen synthesis of fibroblasts.

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