CircRNAs, a type of non-coding RNA widely present in eukaryotic cells, have emerged as a prominent focus in tumor research. However, the functions of most circRNAs remain largely unexplored. Known circRNAs exert their regulatory roles through various mechanisms, including acting as microRNA sponges, binding to RNA-binding proteins, and functioning as transcription factors to modulate protein translation and coding. Tumor growth is not solely driven by gene mutations but also influenced by diverse constituent cells and growth factors within the tumor microenvironment (TME). As crucial regulators within the TME, circRNAs are involved in governing tumor growth and metastasis. This review highlights the role of circRNAs in regulating angiogenesis, matrix remodeling, and immunosuppression within the TME. Additionally, we discuss current research on hypoxia-induced circRNAs production and commensal microorganisms’ impact on the TME to elucidate how circRNAs influence tumor growth while emphasizing the significance of modulating the TME.

This study aimed to investigate the potential association between white blood cell counts and the risk of lung cancer, including its subtypes, through Mendelian randomization (MR) analysis. We conducted a two-sample MR analysis using genome-wide association study (GWAS) summary statistics for the both exposure traits (eosinophil count, neutrophil count, lymphocyte count, monocyte count, basophil count, and total white blood cell count) and outcome traits (lung cancer and its subtypes). The GWAS dataset for lung cancer included 29,266 cases (11273 lung adenocarcinoma (LUAD), 7426 lung squamous cell carcinoma (LSCC), 2664 small cell lung cancer (SCLC)) and 56,450 controls. In MR analysis, we employed methods such as Inverse variance weighted (IVW), weighted median, MR-Egger regression, MR pleiotropy residual sum and outlier. MR analysis revealed an elevated total white blood cell (WBC) count significantly increased the risk of LUAD (IVW: OR = 1.484, 95% CI = 1.219–1.749, p = 0.003). The results confirmed a causal relationship between monocyte count and LUAD (IVW: OR = 1.687, 95% CI:1.542–1.830, p < 0.001). An increased total WBC count was associated with a higher risk of LUAD. Additionally, analysis of WBC subtypes counts indicated that monocyte count plays an crucial role in the elevated risk of LUAD.

Background: The long non-coding RNA cancer susceptibility candidate (CASC) has abnormal expression in lung cancer tissues and may correlate with lung cancer prognosis. This study aimed to comprehensively evaluate the association between CASC expression and the cancer prognosis. Methods: PubMed, Embase, Web of Science, Google Scholar, Cochrane Library, and China National Knowledge Infrastructure databases were searched until April 1, 2023, to obtain the relevant literature. Studies that met the predefined eligibility criteria were included, and their quality was independently assessed by 2 investigators according to the Newcastle-Ottawa Scale (NOS) score. Detailed information was obtained, such as first author, year of publication, and number of patients. Hazard ratio (HR) with a 95% confidence interval (CI) was extracted and grouped to assess the relationship between CASC expression and cancer prognosis. The dichotomous data was merged and shown as the odds ratio (OR) with a 95% CI was extracted to assess the relationship between CASC expression and clinicopathological parameters. Results: A total of 12 studies with 746 patients with lung cancer were included in the meta-analysis. The expression levels of lncRNA CASC2 and CASC7 were decreased, while those of CASC9, 11, 15, and 19 were induced in lung cancer tissues compared with paracancerous tissues. In the population with low CASC expression (CASC2 and CASC7), high CASC expression indicated a good lung cancer prognosis (HR = 0.469; 95% CI, 0.271–0.668). Conversely, in the population with high CASC expression (CASC9, 11, 15, and 19), high CASC expression predicted a poor lung cancer outcome (HR = 1.910; 95% CI, 1.628–2.192). High CASC expression also predicted worse disease-free survival (DFS) (HR = 2.803; 95% CI, 1.804–6.319). Combined OR with 95% CI revealed an insignificant positive association between high CASC expression and advanced TNM stage (OR = 1.061; 95% CI, 0.775–1.454), LNM (OR = 0.962; 95% CI, 0.724–1.277), tumor size (OR = 0.942; 95% CI, 0.667–1.330), and histological grade (OR = 1.022; 95% CI, 0.689–1.517). Conclusion: The CASC expression levels negatively correlate with lung cancer prognosis. Therefore, CASC expression may serve as a prognostic marker and a potential therapeutic target for lung cancer.

Chemotherapy resistance in lung adenocarcinoma (LUAD) limits clinical efficacy. In this study, we first established circ_IGF2BP1 knockdown models in LUAD cells (A549 and H1299). Using dual-luciferase reporter assays, functional analyses, and miR-885-3p rescue experiments, we demonstrated that circ_IGF2BP1 promotes LUAD cell proliferation, migration, and invasion by directly targeting miR-885-3p. Subsequent TargetScan database predictions identified thymidine kinase 1 (TK1) as a downstream target of miR-885-3p. Given the reported roles of miR-885-3p and TK1 in chemoresistance, we generated cisplatin-resistant LUAD cells (A549/DDP) and compared them with cisplatin-sensitive A549 controls. Overexpression or knockdown of circ_IGF2BP1 in these cell lines, combined with dual-luciferase reporter assays, Western blotting, functional studies, and miR-885-3p/TK1 rescue experiments, revealed that the circ_IGF2BP1/miR-885-3p/TK1 axis regulates malignant phenotypes and chemoresistance in both A549 and A549/DDP cells by modulating DNA damage and apoptosis. Furthermore, TK1 overexpression or knockdown in cisplatin-resistant cells confirmed its functional role in LUAD chemoresistance through cellular assays. In addition, qRT-PCR and clinical correlation analyses revealed that circ_IGF2BP1, miR-885-3p, and TK1 are closely associated with clinical diagnosis, prognosis, and treatment in LUAD patients. Collectively, these findings indicate that circ_IGF2BP1 modulates malignant phenotypes and cisplatin resistance in LUAD via the miR-885-3p/TK1 axis by regulating DNA damage and apoptosis pathways.

Lung cancer, with non-small cell lung cancer (NSCLC) representing 85 % of cases, has high global incidence and mortality. Early detection is challenging, often leading to late-stage diagnosis and missed surgical opportunities, highlighting the need for novel biomarkers and therapeutic targets. CircRNA sequencing identified a novel 643-nt circRNA, circ_GLS, which was significantly downregulated in tumors. Functional assays including CCK-8, colony formation, transwell, and wound healing assays, along with xenograft models, demonstrated that circ_GLS inhibits proliferation, migration, and invasion of NSCLC cells in vitro and in vivo. RNA pull-down with RT-qPCR and dual-luciferase assays confirmed direct binding between circ_GLS and miR-410-3p, and between miR-410-3p and GSK3beta. Rescue experiments involving miR-410-3p and GSK3beta validated the role of the circ_GLS/miR-410-3p/GSK3beta/beta-catenin axis in the malignant phenotype, and further experiments elucidated mechanisms via cell cycle, apoptosis, ferroptosis, and epithelial-mesenchymal transition (EMT) modulation. Clinical and bioinformatic analyses revealed that circ_GLS was significantly downregulated in NSCLC tissues, while miR-410-3p was significantly upregulated and GSK3beta downregulated, correlating with diagnosis and prognosis, though independent validation is needed. In conclusion, this study demonstrates for the first time in NSCLC that this axis regulates malignancy, suggesting their potential as therapeutic targets and biomarkers, although challenges in targeting circRNAs remain.

Background: Antifungal therapy is a common treatment option for pulmonary aspergillosis, but its use to prevent recurrence and relieve symptoms in patients with pulmonary aspergillosis remains controversial. This study aimed to explore the short-term efficacy and cost of itraconazole vs. voriconazole in the treatment of pulmonary aspergillosis during the perioperative period.Methods: We retrospectively collected the clinical data of 55 patients with pulmonary aspergillosis who underwent surgery and received itraconazole or voriconazole as antifungal therapy between January 1, 2016, and October 31, 2022, at the Department of Thoracic Surgery, Affiliated Hospital of Zunyi Medical University. We analyzed the effects of different antifungal therapies on the incidence of adverse events, short-term efficacy, and cost-effectiveness of pulmonary aspergillosis treatment.Results: Except for the younger average age of patients in the itraconazole group, there were no significant differences in baseline characteristics such as sex, BMI, underlying lung disease, accompanying symptoms, and lesion location between the voriconazole and itraconazole groups. There was no significant difference in the incidence of adverse events or short-term efficacy, including recovery, symptom improvement, and recurrence rates, during the administration of the antifungal regimens between the two groups. Regarding economic cost efficiency, there was no significant difference in the median hospitalization costs between the two groups. However, despite the longer antifungal treatment duration in the itraconazole group, the cost of itraconazole was significantly lower than that of voriconazole.Conclusion: Both itraconazole and voriconazole effectively prevented the recurrence of pulmonary aspergillosis. They are similar in terms of the incidence of adverse events and short-term efficacy; however, itraconazole is more economical.