Novel insights into molecular patterns of ROS1 fusions in a large Chinese NSCLC cohort: a multicenter study.

ROS proto-oncogene 1, receptor tyrosine kinase (ROS1) rearrangements are a crucial therapeutic target in non-small cell lung cancer (NSCLC). However, there is limited comprehensive analysis of the molecular patterns of ROS1 fusions. This study aimed to address this gap by analysing 135 ROS1 fusions from 134 Chinese NSCLC patients using next-generation sequencing (NGS). The fusions were categorized into common and uncommon based on their incidence. Our study revealed, for the first time, a unique distribution preference of breakpoints within ROS1, with common fusions occurring in introns 31-33 and uncommon fusions occurring in introns 34 and 35. Additionally, we identified previously unknown breakpoints within intron 28 of ROS1. Furthermore, we identified a close association between the distribution patterns of fusion partners and breakpoints on ROS1, providing important insights into the molecular landscape of ROS1 fusions. We also confirmed the presence of inconsistent breakpoints in ROS1 fusions between DNA-based NGS and RNA-based NGS through rigorous validation methods. These inconsistencies were attributed to alternative splicing resulting in out-of-frame or exonic ROS1 fusions. These findings significantly contribute to our understanding of the molecular characteristics of ROS1 fusions, which have implications for panel design and the treatment of NSCLC patients with ROS1 rearrangements.

LncRNA LINC00511 plays an oncogenic role in lung adenocarcinoma by regulating PKM2 expression via sponging miR-625-5p.

BACKGROUND: Lung adenocarcinoma (LAC) is the most prominent histological subtype of non-small cell lung cancer (NSCLC) with a high rate of mortality and metastasis. Accumulating evidence has shown that long non-coding RNAs (lncRNAs) play malfunctioning roles in the development of human tumors. Hence, this study aimed to determine the biological function of LINC00511 in LAC and to provide a novel diagnostic and therapeutic target for it. METHODS: LINC00511 expression in LAC tissues and cell lines (H1299 and A549) were detected by real time-polymerase chain reaction (RT-qPCR). Cell counting kit-8 (CCK-8) assay was employed to analyze cell proliferative ability. Cell metastasis change was measured using transwell assay. Moreover, we revealed a novel target gene of LINC00511 and elucidated the underlying competitive endogenous RNA regulatory mechanism in LAC cells. RESULTS: Data from our study demonstrated that LINC00511 expression was increased in LAC tissues and cells in comparison to their corresponding controls. Moreover, overexpression of LINC00511 indicated the poor prognosis of LAC patients. Overexpression of LINC00511 promoted proliferation, invasion and migration capacities of LAC cells. Moreover, LINC00511 promoted LAC progression via serving as a sponge of miR-625-5p and regulating PKM2 expression. CONCLUSIONS: The present study showed that LINC00511 was involved in LAC progression by targeting miR-625-5p/PKM2, indicating that LINC00511/miR-625-5p/PKM2 may function as promising therapeutic targets for LAC.

Thrombin promotes proliferation of human lung fibroblasts via protease activated receptor-1-dependent and NF-κB-independent pathways.

Acute and chronic respiratory diseases are associated with abnormal coagulation regulation and fibrolysis. However, the detailed mechanism by which coagulation regulation and fibrolysis affect the occurrence and development of lung diseases remain to be elucidated. Protease activated receptor-1 (PAR-1), a major high-affinity thrombin receptor, and nuclear factor kappa B (NF-κB), a transcription factor, are involved in cell survival, differentiation, and proliferation. We have investigated the potential mechanism of thrombin-induced fibroblast proliferation and roles of PAR-1 and NF-κB signalling in this process. The effect of thrombin on proliferation of human pulmonary fibroblasts (HPF) was assessed by 5-bromo-2-deoxyuridine (BrdU) incorporation assay. The expression of PAR1 and NF-κB subunit p65 protein was detected by Western blot. Nuclear translocation of p65 was examined by laser scanning confocal microscopy. We show that thrombin significantly increased proliferation of HPF as determined by induction of BrdU-positive incorporation ratio. Induced PAR1 protein expression was also seen in HPF cells treated with thrombin. However, thrombin had no significant effect on expression and translocation of NF-κB p65 in HPF cells. The results indicate that, by increasing protein expression and interacting with PAR1, thrombin promotes HPF proliferation. NF-κB signalling appears to play no role in this process.