Chronic obstructive pulmonary disease (COPD) is a pathological inflammatory condition of the lungs that is associated with high rates of mortality. Although long non-coding RNAs (lncRNAs) serve a role in lung diseases, their functions in COPD pathogenesis are relatively unknown. The present study aimed to assess the role of differentially expressed lncRNAs in COPD. Expression profile analysis of six lncRNAs in age-matched COPD and non-COPD tissues were conducted. Among the six tested lncRNAs, metastasis-associated in lung adenocarcinoma transcript 1 (MALAT1) was the most consistently overexpressed in COPD lung tissue specimens. To model COPD in vitro, human lung fibroblasts were treated with transforming growth factor-β (TGF-β) and MALAT1 was knocked down by small interfering RNA. This promoted cell viability and concurrently inhibited the expression of mesenchymal proteins, fibronectin and α-smooth muscle actin. In COPD, cell senescence is linked to the activation of mammalian target of rapamycin complex 1 (mTORC1). Upon gene silencing of MALAT1 in non-TGF-β-treated cells, cells demonstrated constitutive activation of mTORC1, which was assessed by the protein expression levels of mTORC1 substrate S6 kinase (S6K1). By contrast, upon MALAT1 silencing in the TGF-β-treated cells, mTORC1 activation was not suppressed, despite the mesenchymal cell markers protein expression levels being downregulated. Thus, lncRNA MALAT1 may represent a potent biomarker in COPD patients and may act as a target for both diagnostic and therapeutic purposes.

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Our results indicated that urinary DNA measurements can potentially be useful for disease monitoring of minimal residual disease (MRD) in NSCLC. This can complement current serial radiographic imaging to provide early detection for lung cancer relapse.

The present study investigated the expression of microRNA (miR)-215 in non-small cell lung carcinoma (NSCLC) at tissue and cellular levels, as well as its biological functions and mechanism of action. A total of 56 patients with NSCLC were included in the present study. NSCLC tissues and tumor-adjacent normal tissues were resected and collected. Reverse transcription-quantitative polymerase chain reaction was used to measure the expression of miR-215. Following transfection with miR-215 mimics, A549 cell proliferation, migration and invasion were determined using a Cell Counting Kit-8 and Transwell assay. Western blotting was employed to measure the expression of matrix metalloproteinase (MMP)-16 protein. A dual-luciferase reporter assay was conducted to determine the existence of a direct interaction between miR-215 and the MMP-16 gene. Reduced expression of miR-215 in NSCLC was closely associated with lymphatic metastasis and TNM staging. Overexpression of miR-215 inhibited the proliferation of A549 cells in vitro. Upregulated expression of miR-215 inhibited the migration and invasion of A549 cells in vitro. miR-215 exerted its biological functions possibly by regulating the expression of MMP-16. Elevated expression of MMP-16 promoted the proliferation, migration and invasion of A549 cells. miR-215 regulated the proliferation, migration and invasion of A549 cells by binding with the seed 3′-untranslated region of MMP-16 mRNA. The present study demonstrates that reduced expression of miR-215 in NSCLC is negatively associated with lymphatic metastasis and TNM staging. In addition, miR-215 acts as a tumor suppressor gene by inhibiting the proliferation, migration and invasion of NSCLC cells via the downregulation of MMP-16 expression.

Background Somatic mutations are important biomarkers for selecting an optimal targeted therapy and predicting outcomes for non-small-cell lung cancer (NSCLC) patients that are often detected from tissue samples. However, tissue samples are not always readily available from these patients. The exploration of using circulating tumor DNA (ctDNA) to identify somatic mutations offers an alternative source that should be explored. Methods In this retrospective study, we included 280 patients diagnosed with adenocarcinoma between 2017 and 2018 in a hospital in eastern China. Tissue or ctDNA was collected, and a wide spectrum of somatic mutations was analyzed by targeted next-generation sequencing platforms. Associations among the mutation status, biomarkers, screening methods, disease stages, and interaction with treatment with overall survival (OS) were investigated. Results We found that the EGFR L858R mutation was the most frequently identified mutation in adenocarcinoma in this population by both methods, followed by KRAS (p=3.7e-09), PIK3CA (p=5e-04), and HER2 mutations (p=6.3e-03). We observed that EGFR mutations were significantly mutually exclusive with KRAS, HER2, and MET. FGFR1 mutations were significantly more abundantly detected in the ctDNA group. We found an interaction effect between EGFR mutation and target therapies. The ability of the targeted therapy to improve OS in patients with a single EGFR mutation (HR=0.069, p=0.07) approached significance, but this was not the case for the patients with more than one EGFR mutation or without an EGFR mutation (HR=0.813, p=0.725). Furthermore, the effect of chemotherapy was more predominant in the EGFR group in comparison to the control group. Conclusion These findings provide useful information on the distribution of somatic mutations via different screening methods and how this related to the optimal treatment selection in Chinese patients with NSCLC.