Lung cancer is one of the common malignant tumors that threaten human life with serious incidence and high mortality. According to the histopathological characteristics, lung cancer is mainly divided into non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC). NSCLC accounts for about 80-85% of lung cancers. In fact, lung cancer metastasis is a major cause of treatment failure in clinical patients. The underlying reason is that the mechanisms of lung cancer metastasis are still not fully understood. The metastasis of lung cancer cells is controlled by many factors, including the interaction of various components in the lung cancer microenvironment, epithelial-mesenchymal transition (EMT) transformation, and metastasis of cancer cells through blood vessels and lymphatics. The molecular relationships are even more intricate. Further study on the mechanisms of lung cancer metastasis and in search of effective therapeutic targets can bring more reference directions for clinical drug research and development. This paper focuses on the factors affecting lung cancer metastasis and connects with related molecular mechanisms of the lung cancer metastasis and mechanisms of lung cancer to specific organs, which mainly reviews the latest research progress of NSCLC metastasis. Besides, in this paper, experimental models of lung cancer and metastasis, mechanisms in SCLC transfer and the challenges about clinical management of lung cancer are also discussed. The review is intended to provide reference value for the future research in this field and promising treatment clues for clinical patients.

Macrophages has become a promising target of sepsis treatment because macrophages dysfunction contributes to the progress of sepsis. The targeted therapy of sepsis based on macrophages ferroptosis is drawing more and more attention, but the molecular mechanism involved is poorly understood. In this study, Mus musculus-derived macrophages were used for in-vitro experiments. We found that LPS could induce ferroptosis in macrophages via the detection of apoptosis, GSH, lipid peroxide and GPX4 levels. Meanwhile, miR-129-2-3p was up-regulated in macrophages exposure to LPS. Next, we confirmed that miR-129-2-3p promoted the LPS-induced polarization of M1 phenotype in macrophages via the detection of Arg-1 and iNOS levels; miR-129-2-3p promoted the LPS-induced ferroptosis in macrophages. Further, luciferase assay showed that SMAD3 was identified as a target gene of miR-129-2-3p and its expression was negatively regulated by miR-129-2-3p and LPS. SMAD3 could inhibit the LPS-induced polarization of M1 phenotype and ferroptosis in macrophages by targeting GPX4. Collectively, we demonstrated the target gene and molecular mechanism of miR-129-2-3p mediating LPS-induced polarization and ferroptosis in macrophages by targeting the SMAD3-GPX4 axis, which would provide a novel strategy for sepsis targeted therapy based on macrophages polarization and ferroptosis.

Editorial: Epigenetics in Cancer: Mechanisms and Drug Development

Background: We aimed to investigate the effect of 4-methyl-N-(piperidin-1-ylmethylene) benzenesulfonamide (PMSA) on tumor cell proliferation, migration, ferroptosis, and the potential molecular mechanism of ferroptosis in tumor cells. Methods: PMSA was produced in the marine biomedical research institute of Guangdong Medical University (Zhanjiang, China) and used for tumor cells treatment. MTT and cell colony formation assays were used to measure the inhibition of tumor cell proliferation, the scratch assay was used to identified the suppression of tumor cell migration, the death of tumor cells was measured by Annexin-V-FITC/PI staining, the level of ferroptosis-relative lipid ROS in tumor cells was measured by flow cytometry and MDA detection kit, and the expression of ferroptosis-relative protein was measured by Western blot. The Discovery Studio system was used for molecular docking and the binding ability was measured by cellular thermal shift assay. Results: The PMSA we produced inhibited tumor cell proliferation, colony formation, migration and triggered cell death, and Fer-1 could reverse these effects. The amount of ROS and MDA levels in tumor cells was also markedly raised by PMSA. PMSA treatment significantly reduced the expression of SLC7A11/XCT, NRF2, and GPX4 in tumor cells. The phosphorylation level of NRF2 was also decreased. Through molecular docking, it was discovered that PMSA could bind to NRF2 and thereby block its activity. Conclusion: The KEAP1-NRF2-GPX4 axis was the target of PMSA’s anti-tumor action, which results in ferroptosis of tumor cells. This demonstrated that the compound has the potential to be used as a candidate for anti-tumor drugs.