Shirong Li

As a malignant tumor with high morbidity and mortality, lung cancer is associated with a variety of risk factors, including smoking, exposure to occupational carcinogens, familial inheritance, and chronic lung disease. Lung cancer is often detected late and has a complex pathogenesis, so early diagnosis and intervention of lung cancer are essential. Finding effective targets is important to develop new treatments for lung cancer. As a member of Group 4A of the nuclear receptor subfamily, Nuclear Receptor Subfamily 4 Group A Member 1 (NR4A1) is an immediate early gene that encodes a transcription factor that plays a regulatory role when the cell and tissue microenvironment changes. NR4A1 plays a pro-cancer role in solid tumors including lung cancer, but a tumor suppressor role in hematological malignancies. NR4A1 palys a role through multiple mechanisms in lung cancer, including promoting cell proliferation by forming a complex with p300/specific protein 1 (Sp1) and acting on the survivin and AMP-activated protein kinase (AMPK)/mechanistic Target of Rapamycin Complex 1 (mTORC1) pathways, promoting metastasis and invasion by inducing the occurrence of transforming growth factor-β (TGF-β) dependent epithelial-mesenchymal transition (EMT), promoting vascular remodeling by acting on vascular endothelial growth factor A (VEGF-A), promoting immune escape by acting on programmed cell death-1 (PD-1) dependent T cell exhaustion, promoting cell apoptosis interacted with B-cell lymphoma-2 (Bcl-2) and promoting metabolic reprogramming by increasing fatty acid oxidation. In recent years, several studies on NR4A1-related agonists and inhibitors in lung cancer have been reported. These compounds are expected to become drugs for targeted tumor therapy, but current research is limited to cellular and animal experiments. It still takes time to verify and evaluate clinical applications, other biological effects and potential side effects. This review summarizes the biological role of NR4A1 in lung cancer and describes the molecular mechanisms and signaling pathways regulated by NR4A1. This paper will provide a theoretical basis for the early treatment of lung cancer by using NR4A1-related compounds in the clinic.

Background: Non-small cell lung cancer (NSCLC) is the most common type of lung cancer (LC), which is the leading cause of tumor mortality. In recent years, compared with tissue biopsy, which is the diagnostic gold standard for tumor diagnosis, Liquid biopsy (LB) is considered to be a more minimally invasive, sensitive, and safer alternative or auxiliary diagnostic method. However, the current value of LB in early diagnosis of LC is not ideal, so it is particularly important to study the changes in blood composition during the process of tumorigenesis and find more sensitive biomarkers. Purpose: Platelets are a type of abundant blood cells that carry a large amount of RNA. In the LC regulatory network, activated platelets play an important role in the process of tumorigenesis, development, and metastasis. In order to identify predictive liquid biopsy biomarkers for the diagnosis of NSCLC, we summarized the development and function of platelets, the interaction between platelets and tumors, the value of TEP RNA in diagnosis, prognosis, and treatment of NSCLC, and the method for detecting TEP RNA of NSCLC in this article. Conclusion: The application of platelets in the diagnosis and treatment of NSCLC remains at a nascent stage. In addition to the drawbacks of low platelet count and complex experimental processes, the diagnostic accuracy of TEP RNA-seq for cancer in different populations still needs to be improved and validated. At present, a large number of studies have confirmed significant differences in the expression of TEP RNA in platelets between NSCLC patients and healthy individuals. Continuous exploration of the diagnostic value of TEP RNA in NSCLC is of utmost importance. The integration of NSCLC platelet-related markers with other NSCLC markers can improve current tumor diagnosis and prognostic evaluation systems, providing broad prospects in tumor screening, disease monitoring, and prognosis assessment.

Supplementary Figures 1. Analysis of eIF4E protein levels by western blotting of whole cell extracts from primary stromal cells, CD138- cells, primary myeloma cells (CD138+) and normal plasma cells. Supplementary Figures 2. CT shRNA, eIF4E shRNA, PCDH-GFP or PCDH-eIF4E U266 cells were analyzed by Annexin V binding/ PI staining for apoptotic cells.

Lung cancer (LC) is the leading cause of cancer‑related death, with high incidence and mortality rate. Early diagnosis and treatment of LC are imperative to improve the 5‑year survival rate for patients with LC. In recent years, miRNAs as promising biomarkers with high sensitivity and specificity for LC have been studied increasingly. In LC regulatory networks, miRNAs play crucial roles in the occurrence, development and metastasis of non‑small cell lung cancer (NSCLC), such as oncogenic factors, tumor suppressors and regulators. Dysfunctional miRNAs perform tumor‑suppressive or oncogenic functions in the regulation of cell proliferation, invasion, apoptosis, cell cycle disorder and angiogenesis by negatively regulating target genes. In the present review, the biological process of miRNAs was firstly summarized and recent advances in the mechanism of miRNAs involved in tumor formation and development were described. In addition, the present review concentrated on the latest findings on the miRNAs related with circulating free and extracellular vesicles in the early diagnosis of NSCLC. Additionally, the diagnostic performances of circulating free and extracellular vesicles‑associated miRNAs in NSCLC were contrasted. Owing to the increased stability and wide‑ranging practical applicability, miRNA may be one promising biomarker for NSCLC diagnosis.

Introduction. The emergence of antibiotic-resistant Salmonella isolates is a global concern and has been attributed to the indiscriminate use of antibiotics in humans and animals. Integrons are mobile gene elements closely related to bacterial drug resistance. Among them, class 1 integrons containing various resistance gene cassettes could play an important role in disseminating and maintaining antibiotic resistance in Salmonella isolates. Hypothesis. Salmonella class 1 integrons have a relationship with Salmonella drug resistance. Aim. This study aims to investigate the distribution of class 1 integrons and their variable regional molecular characteristics, as well as the diversity of the promoters and drug sensitivity among Salmonella strains. Methodology. A total of 111 Salmonella strains, collected between 2018 and 2020, underwent fully automated bacterial identification using the VITEK 2 Compact system and an antibiotic sensitivity test. PCR was employed to screen class 1 integrase genes (IntI1) and integron variable regions, while promoter type and variable region gene cassette characteristics were determined using sequencing analysis. Results. A total of 24 IntI1-positive strains were detected in 111 Salmonella strains. Moreover, IntI1-positive strains exhibited statistically significant resistance to ceftazidime, ciprofloxacin, levofloxacin, ceftriaxone, trimethoprim/sulfamethoxazole and azithromycin compared to integron-negative strains (PIntI1-positive strains was significantly higher than that of negative strains. Variable regions were observed in 6 of the 24 IntI1-positive strains. Four gene cassettes were detected, namely dfrA17-aadA5, dfrA12-aadA2, aadA22 and aar-3-dfrA27. Finally, 3 types of class 1 integron variable region promoters were identified in 24 strains, including PcW, PcH1 and PcW_TGN-10; they are all relatively weak promoters. Conclusion. The integron and the drug resistance genes carried by integron have a certain relationship with drug resistance.