The long noncoding RNA ANRIL acts as an oncogene and contributes to paclitaxel resistance of lung adenocarcinoma A549 cells

Neuroendocrine regulatory polypeptide VGF (nerve growth factor inducible) was firstly found in the rapid induction of nerve growth factor on PC12 cells. It was selectively distributed in neurons and many neuroendocrine tissues. This paper reviewed the latest literatures on the gene structure, transcriptional regulation, protein processing, distribution and potential receptors of VGF. The neuroendocrine roles of VGF and its derived polypeptides in regulating energy, water electrolyte balance, circadian rhythm and reproductive activities were also summarized. Furthermore, based on the experimental evidence in vivo and in vitro, dysregulation of VGF in different neuroendocrine diseases and the possible mechanism mediated by VGF polypeptides were discussed. We next discussed the potential as the clinical diagnosis and therapy for VGF related diseases in the future.

Nucleotide‐binding and oligomerization domain‐containing protein 2 (NOD2) was a member of the NOD‐like receptor family and played an important role in the innate immune response. Dysregulated NOD2 had been reported to contribute to tumorigenesis and progression. Here, we investigated that decreased NOD2 expressions could affect the phenotypic polarization of tumour‐associated macrophages and thus lead to the poor prognosis of lung adenocarcinoma patients. We clustered the patients by the single‐sample gene set enrichment analysis of tumour microenvironment and 13 prognostic differentially expressed immune‐related genes (PDEIRGs) were obtained based on prognostic analyses. After multiple assessments on the 13 PDEIRGs, NOD2 was considered to be the central immune gene and had a strong effect on suppressing tumour progression. Decreased NOD2 expression could be induced by cancer cells and lead to the phenotypic polarization of macrophages from protective M1 phenotype to pro‐tumorigenic M2 subtype which might be attributed to the down‐regulating of NF‐κB signalling pathway. This study draw attention to the role of inhibited innate immune function mediated by depletion of NOD2 in the TME. Our work also points to a potential strategy of NOD2‐mediated TAM‐targeted immunotherapy.

Phytochemical investigation on the 70% EtOH extract of the roots of Thalictrum foliolosum DC. resulted in the isolation of three new isoquinoline alkaloids, 5,6,7,12-tetramethoxy-2-methyl-13-hydroxy-11-(4′-methoxycarbonylphenoxy)benzylisoquinoline (1), 5,6,7,12-tetramethoxy-2-methyl-13-hydroxy-11-(4′-carbonylphenoxy) benzylisoquinoline (2), and 3-methoxy-10-O-acetylprodensiflorin B (3). The new structures were elucidated by using spectroscopic data (NMR, IR, UV, and MS). The isolated alkaloids were tested in vitro for cytotoxic potentials against six human lung cancer cell lines (H460, H23, HTB-58, A549, H441, and H2170). As a result, alkaloids 1 and 2 exhibited significant cytotoxic activities against all the tested tumor cell lines with IC₅₀ values less than 20 μM.

Background: Image-based screening improves the detection of early-stage lung adenocarcinoma (LUAD)but also highlights the issue of high false-positive diagnoses, which puts patients at a risk of unnecessary over-treatment. Therefore, more precise discrimination criteria are required to ensure that patients with early-stage LUAD receive appropriate treatments. Methods: We integrated 158 early-stage LUAD cases from 2 independent cohorts, including 30 matched resected specimens with complete radiological and pathological information, and 128 retrospective pathological pair-samples with partial follow-up data. This integration allowed us to conduct a correlation analysis between clinical phenotype and transcriptome landscape. Immunohistochemistry was performed using tissue microarrays to examine the expression of phospholipid phosphatase 2 (PLPP2) and lipid-raft markers. Lipidomics analysis was used to determine the changes of lipid components in PLPP2-overexpressed cells. To assess the effects of PLPP2 on the malignant phenotypes of LUAD cells, we conducted mice tumor-bearing experiments and in vitro cellular experiments by knocking down PLPP2 and inhibiting lipid raft synthesis with MβCD, respectively. Results: Bioinformatics analysis indicated that the co-occurrence of lipid raft formation and rapid cell proliferation might exhibit synergistic effects in driving oncogenesis from lung preneoplasia to adenocarcinoma. The enhanced activation of the cell cycle promoted the transition from non-invasive to invasive status in early-stage LUAD, which was related to an increase in lipid rafts within LUAD cells. PLPP2 participated in lipid raft formation by altering the component contents of lipid rafts, such as esters, sphingomyelin, and sphingosine. Furthermore, elevated PLPP2 levels were identified as an independent prognostic risk factor for LUAD patients. Further results from in vivo and in vitro experiments confirmed that PLPP2 could induce excessive cell proliferation by enhancing lipid raft formation in LUAD cells. Conclusions: Our study has revealed the characteristics of gene expression profiles in early-stage LUAD patients with the different radiological and pathological subtypes, as well as deciphered transcriptomic evolution trajectory from preneoplasia to invasive LUAD. Furthermore, it suggests that PLPP2-mediated lipid raft synthesis may be a significant biological event in the initiation of early-stage LUAD, offering a potential target for more precise diagnosis and therapy in clinical settings.

Elevated fibrous sheath interacting protein 1 levels are associated with poor prognosis in non-small cell lung cancer patients Elevated fibrous sheath interacting protein 1 levels are associated with poor prognosis in non-small cell lung cancer patients