Microplastics exposure causes the senescence of human lung epithelial cells and mouse lungs by inducing ROS signaling.

Microplastics (MPs) are environmental pollutants and can be inhaled by humans to threaten health. The lung tissue, responsible for the gas exchange between the body and the environment, is vulnerable to MPs exposure. However, from the perspective of cellular senescence, the effect of MPs on lung cells and tissues has not yet been deeply dissected. In this study, we reported that all the four typical MPs exhibited the significant biological effects in term of inducing senescence of human lung derived cells A549 and BEAS-2B in vitro. We further found that polyvinyl chloride (PVC) increased the reactive oxygen species (ROS) level in A549 cells and that PVC-induced senescent characteristics could be largely reversed by antioxidant treatment. Importantly, intratracheal instillation of PVC MPs in mice could effectively impair their physical function, induce the increased systemic inflammation level, cause the accumulation of senescent cells. Our study demonstrates that MPs induce senescence in human lung epithelial cells and mouse lungs by activating ROS signaling, and provides new insight into the potential pathogenesis of MPs on lung diseases.

Long Noncoding RNA Regulator of Reprogramming Regulates Cell Growth, Metastasis, and Cisplatin Resistance in Gastric Cancer via miR-519d-3p/HMGA2 Axis.

Background: Gastric cancer (GC) is a common tumor found worldwide, and cisplatin is the first-line agent for the treatment of GC. However, the resistance to cisplatin is an obstacle. Here, we explored the biological mechanism of long noncoding RNA regulator of reprogramming (ROR) in the cisplatin resistance of GC. Materials and Methods: ROR, miR-519d-3p, and high mobility group protein A2 (HMGA2) expression in GC tissues and cells were measured by quantitative real-time polymerase chain reaction and Western blot. Cell viability, migration, invasion, and apoptosis were detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay, transwell assay, and flow cytometry, respectively. The relative protein expression was detected by Western blot. The interactions between miR-519d-3p and ROR, HMGA2 were predicted using miRcode and starBase v2.0 online database, and then verified by dual luciferase reporter assay and RNA immunoprecipitation assay. In addition, the xenograft tumor mouse model was constructed to verify the biological role of ROR in vivo. Results: The levels of ROR, HMGA2 were significantly upregulated, and miR-519d-3p was apparently downregulated in GC tissues and cells. The miRcode and starBase v2.0 online websites and dual luciferase reporter assay validated that miR-519d-3p directly interacted with ROR and HMGA2. Furthermore, ROR knockdown downregulated HMGA2 to restrain cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and cisplatin resistance in GC cells by targeting miR-519d-3p. In addition, the depletion of ROR repressed the xenograft tumor growth in vivo. Conclusion: In conclusion, we first found the ROR/miR-519d-3p/HMGA2 regulatory network to regulate cell proliferation, migration, invasion, EMT, and cisplatin resistance in GC, and this may shed light on the GC tumorigenesis.

Linkage of a locus determining familial progressive hyperpigmentation (FPH) to chromosome 19p13.1-pter in a Chinese family.

Familial progressive hyperpigmentation (FPH) is a rare autosomal dominantly inherited disorder characterized by patches of hyperpigmentation in the skin which are present at birth or in early infancy and increase in size and number with age. Although previous studies showed that FPH is a monogenic trait, the genetic basis for this disease is unknown. Using a genome screening with 182 STR markers from autosomes in a three-generation Chinese family with 17 members, including 6 affected individuals, we identified a locus linked to chromosome 19p13.1-pter responsible for FPH, spanning 45.48 cM between D19S593 and 19pter. Interestingly, this region harbors the LKB1 gene, in which germline mutations were shown to be associated with Peutz-Jeghers Syndrome (PJS). PJS and FPH share the disorder of hyperpigmentation, the fine mapping of the FPH gene is expected to lead to a better understanding of the etiology for both FPH and PJS. The linkage of FPH locus to human chromosome 19p13.1-pter provides a genetic basis for further fine mapping.