Radiation-induced pulmonary fibrosis (RIPF) is a common complication of thoracic tumors, lacking targeted therapeutic strategies, which seriously affects the quality of life. Numerous studies have confirmed that epithelial to mesenchymal transition (EMT) plays an important role in RIPF, but the specific mechanism remains unclear. We verified by mice lung tissue miRNA microarray screen combined with alveolar type II epithelial cells (AECII) and found that miRNA-let-7i was significantly highly expressed after ionizing radiation (IR). It was also confirmed that miRNA-let-7i inhibited its expression by targeted binding to the 3ʹUTR of IL-10, promoting the phosphorylation activation of AKT, and subsequently inducing the EMT of AECII. In conclusion, our study confirmed the role and specific mechanism of miRNA-let-7i promoting AECII cells EMT to participate in RIPF and provided a new target for the prevention and treatment of RIPF.
DNA damage response (DDR) is an intracellular pathway that senses and repairs damaged DNA. Proper regulation of this pathway is essential for maintaining genome stability and promoting cell survival. These repair mechanisms are regulated by multiple nuclear DNA damage repair enzymes, which can scan the DNA for problems and restore the DNA double helix structure. In addition to DDR-involved proteins located in cell nuclei, mitochondrial molecular machinery also coordinate this role; the mitochondria sense fluctuations in specific DNA damage signaling and subsequently activate the effector molecules and appropriate pathway. In this review, we summarized the latest scientific literature regarding molecular mechanisms of mitochondria-mediated stress responses in DNA damage signaling. Additionally, we have described future directions necessary for a comprehensive understanding of mitochondria-DDR signaling networks.
Diseases of female reproductive system include tumor diseases (e.g. breast cancer, ovarian cancer, cervical cancer, endometrial cancer, and uterine fibroids) and non-tumor diseases (e.g. endometriosis, hypertensive disorders complicating pregnancy, and fetal growth restriction). Hypoxia is one of the most important factors that may regulate the occurrence of these diseases. As a key transcription factor under hypoxia, HIF-1 (hypoxia-inducible factor-1) promotes the transcription of a vast amount of downstream genes and regulates the functions and phenotypes of various cells under hypoxia. In this review, we summarize that hypoxia and HIF-1 affect these tumor and non-tumor diseases by regulating various cell invasion, proliferation, apoptosis, autophagy, proliferation or differentiation. We also review the roles of non-coding RNAs in the regulation of various cell dysfunctions under hypoxia. We hope to reveal the roles and regulatory mechanisms of non-coding RNAs in the effects of hypoxia on female reproductive system diseases and to provide potential new approaches for early detection and clinical treatment against female reproductive system diseases.
During ontogeny and adult homeostasis, mechanical forces provide cells with important signals that guide cellular and tissue behavior. In addition, cells receive and transmit mechanical signals through mechanotransduction that control cell proliferation, differentiation, and death. Dysregulation of the mechanical microenvironment and the internal mechanical system of cells can lead to a variety of diseases, including tumors. Meanwhile, genomic instability is one of the key steps in cancer initiation and progression. Although numerous experiments have suggested a link between cellular mechanics and genome instability, the underlying mechanisms are unclear. Here, we discuss how the extracellular mechanical microenvironment, mechanosensing receptors, cytoskeletal systems, and mechanosignaling of nuclear mechanotransduction affect genomic instability.
Chemical carcinogens, which are exogenous DNA-damaging agents, are ubiquitous in both the industry and living environments. The carcinogens pose a threat to the integrity of genetic information by causing diverse types of DNA damage through various pathways. Subsequently, the organism activates a DNA damage response mechanism to repair the damage caused by chemical carcinogens. However, incorrect or ineffective repair processes, along with DNA damage accumulation, may lead to genomic instability and mutations, which play a critical role in carcinogenesis. However, the types of DNA damage induced by a large variety of chemical carcinogens may vary due to the different physicochemical properties of chemicals and ultimately affect the carcinogenic process. In this review, we discuss the mechanisms of DNA damage and ultimately carcinogenesis by various environmental chemical carcinogens, namely heavy metals, polycyclic aromatic hydrocarbons, and aromatic amines. We also summarize the potential types of DNA damage that are closely associated with carcinogens.
Ultraviolet (UV) radiation is one of the major environmental pathogenic factors for mammals and has been identified as a carcinogen for initiating and promoting human skin cancers. As the main chromophore for UV energy, DNA is the direct target and generates abundant photolesions, cyclobutene pyrimidine dimers (CPDs) and pyrimidine–pyrimidone (6–4) photoproducts (6–4PPs). The formation of CPDs and 6–4PPs is sequence specific and di-pyrimidine site is identified as the hotspots. Besides, some epigenetic regulations are involved in this process to influence the yield of photolesions. Upon UV radiation, the photolesions contribute to cell death and are the primary source of mutagenicity. To defend these detrimental effects to cells, DNA repair mechanisms and several signaling transduction pathways are collaborated to remove those photolesions. Nucleotide excision repair (NER) is the prominent way to recognize the damaged sites, excising the photolesions and repairing the DNA strand. Other cell responses have been along with NER system to complete the repair genetically. This review is focused on UV-induced DNA damage and summarizes current advances about the formation of CPDs and 6–4PPs as well as NER system and collaborated cell responses.