Oxidative stress is a state of imbalance between oxidation and antioxidation. Excessive ROS levels are an important factor in tumor development. Damage stimulation and excessive activation of oncogenes cause elevated ROS production in cancer, accompanied by an increase in the antioxidant capacity to retain redox homeostasis in tumor cells at an increased level. Although moderate concentrations of ROS produced in cancer cells contribute to maintaining cell survival and cancer progression, massive ROS accumulation can exert toxicity, leading to cancer cell death. RNA modification is a posttranscriptional control mechanism that regulates gene expression and RNA metabolism, and m⁶A RNA methylation is the most common type of RNA modification in eukaryotes. m⁶A modifications can modulate cellular ROS levels through different mechanisms. It is worth noting that ROS signaling also plays a regulatory role in m⁶A modifications. In this review, we concluded the effects of m⁶A modification and oxidative stress on tumor biological functions. In particular, we discuss the interplay between oxidative stress and m⁶A modifications.

Aberrant expression of the zinc finger protein (ZIC) family has been extensively reported to contribute to progression and metastasis in multiple human cancers. However, the functional roles and underlying mechanisms of ZIC2 in non-small cell lung cancer (NSCLC) are largely unknown. In this study, ZIC2 expression was evaluated using qRT-PCR, western blot, and immunohistochemistry, respectively. Animal experiments in vivo and functional assays in vitro were performed to investigate the role of ZIC2 in NSCLC. Luciferase assays and chromatin immunoprecipitation (ChIP) were carried out to explore the underlying target involved in the roles of ZIC2 in NSCLC. Here, we reported that ZIC2 was upregulated in NSCLC tissues, and high expression of ZIC2 predicted worse overall and progression-free survival of NSCLC patients. Silencing ZIC2 repressed tumorigenesis and reduced the anoikis resistance of NSCLC cells. Mechanical investigation further revealed that silencing ZIC2 transcriptionally inhibited Src expression and inactivated steroid receptor coactivator/focal adhesion kinase signaling, which further attenuated the anoikis resistance of NSCLC cells. Importantly, our results showed that the number of circulating tumor cells (CTCs) was positively correlated with ZIC2 expression in NSCLC patients. Collectively, our findings unravel a novel mechanism implicating ZIC2 in NSCLC, which will facilitate the development of anti-tumor strategies in NSCLC.

Purpose. To establish an effective and accurate prognostic nomogram for lung adenocarcinoma (LUAD). Patients and Methods. 62,355 LUAD patients from 1975 to 2016 enrolled in the Surveillance, Epidemiology, and End Results (SEER) database were randomly and equally divided into the training cohort (n=31,179) and the validation cohort (n=31,176). Univariate and multivariate Cox regression analyses screened the predictive effects of each variable on survival. The concordance index (C-index), calibration curves, receiver operating characteristic (ROC) curve, and area under the ROC curve (AUC) were used to examine and validate the predictive accuracy of the nomogram. KaplanMeier curves were used to estimate overall survival (OS). Results. 10 prognostic factors associated with OS were identified, including age, sex, race, marital status, American Joint Committee on Cancer (AJCC) TNM stage, tumor size, grade, and primary site. A nomogram was established based on these results. C-indexes of the nomogram model reached 0.777 (95 confidence interval (CI), 0.773 to 0.781) and 0.779 (95 CI, 0.775 to 0.783) in the training and validation cohorts, respectively. The calibration curves were well-fitted for both cohorts. The AUC for the 3- and 5-year OS presented great prognostic accuracy in the training cohort (AUC=0.832 and 0.827, respectively) and validation cohort (AUC=0.835 and 0.828, respectively). The KaplanMeier curves presented significant differences in OS among the groups. Conclusion. The nomogram allows accurate and comprehensive prognostic prediction for patients with LUAD.

The correlation between cathepsins and pulmonary arterial hypertension (PAH) is well-established, but the causative link between them remains uncertain. This study aimed to explore the causal role of circulating metabolites mediating cathepsins in PAH using Mendelian randomization (MR). A 2-sample 2-step MR method was used to identify causal relationship between cathepsins and PAH; causal relationship between circulating metabolites and PAH; and mediated effects of these circulating metabolites. GWAS summary statistics on circulating metabolites were from the Canadian longitudinal study on aging cohort, human plasma cathepsins from The INTERVAL study, and PAH from FinnGen version R10. Two-sample MR analyses involving 9 cathepsins (cathepsin B, E, F, G, H, L2, O, S, and Z). Cathepsin S was associated with high risk of PAH (OR: 1.346, 95% CI: 1.039–1.742, P = .024), and positively with circulating metabolite 1-oleoylglycerol (18:1) levels (OR: 1.062, 95% CI: 1.018–1.108, P = .005). Finally, mediation analysis showed evidence of mediated effect of cathepsin S on PAH through 1-oleoylglycerol (18:1) levels (OR: 0.062, CI: 0.0183–0.106) with a mediated proportion of 20.9% of the total effect. This study reveals cathepsin S increases the risk of PAH mediating by circulating metabolite 1-oleoylglycerol (18:1) levels.