Blockade of the lncRNA-DOT1L-LAMP5 axis enhances autophagy and promotes degradation of MLL fusion proteins.

BACKGROUND: Mixed-lineage leukemia (MLL) fusion gene caused by chromosomal rearrangement is a dominant oncogenic driver in leukemia. Due to having diverse MLL rearrangements and complex characteristics, MLL leukemia treated by currently available strategies is frequently associated with a poor outcome. Therefore, there is an urgent need to identify novel therapeutic targets for hematological malignancies with MLL rearrangements. METHODS: qRT-PCR, western blot, and spearman correction analysis were used to validate the regulation of LAMP5-AS1 on LAMP5 expression. In vitro and in vivo experiments were conducted to assess the functional relevance of LAMP5-AS1 in MLL leukemia cell survival. We utilized chromatin isolation by RNA purification (ChIRP) assay, RNA pull-down assay, chromatin immunoprecipitation (ChIP), RNA fluorescence in situ hybridization (FISH), and immunofluorescence to elucidate the relationship among LAMP5-AS1, DOT1L, and the LAMP5 locus. Autophagy regulation by LAMP5-AS1 was evaluated through LC3B puncta, autolysosome observation via transmission electron microscopy (TEM), and mRFP-GFP-LC3 puncta in autophagic flux. RESULTS: The study shows the crucial role of LAMP5-AS1 in promoting MLL leukemia cell survival. LAMP5-AS1 acts as a novel autophagic suppressor, safeguarding MLL fusion proteins from autophagic degradation. Knocking down LAMP5-AS1 significantly induced apoptosis in MLL leukemia cell lines and primary cells and extended the survival of mice in vivo. Mechanistically, LAMP5-AS1 recruits the H3K79 histone methyltransferase DOT1L to LAMP5 locus, directly activating LAMP5 expression. Importantly, blockade of LAMP5-AS1-LAMP5 axis can represses MLL fusion proteins by enhancing their degradation. CONCLUSIONS: The findings underscore the significance of LAMP5-AS1 in MLL leukemia progression through the regulation of the autophagy pathway. Additionally, this study unveils the novel lncRNA-DOT1L-LAMP5 axis as promising therapeutic targets for degrading MLL fusion proteins.

Advanced Luminescence Anticounterfeiting Based on Dynamic Photoluminescence and Non-Pre-Irradiation Mechanoluminescence.

Luminescence anticounterfeiting is one of the most significant technologies to protect information security. However, the luminescence of the present anticounterfeiting logo is static, which is easily counterfeited by substitutes, and it always requires an ultraviolet lamp in use, which is inconvenient in application. In this work, according to the present deficiencies of luminescence anticounterfeiting, an interesting phosphor CaZnGe2O6/Mn2+ with unique features of dynamic photoluminescence and non-pre-irradiation mechanoluminescence is developed for the first time. The photoluminescence color of the phosphor can dynamically change from green to red during irradiation, and the non-pre-irradiation mechanoluminescence of the phosphor-based elastomer can be easily stimulated by mechanics such as stretching, bending, or scratching with a finger. By combining the two features of the CaZnGe2O6/Mn2+ phosphor, an advanced dual-mode luminescence anticounterfeiting is designed, and a luminescence logo is fabricated for the anticounterfeiting test. The result demonstrates that this advanced luminescence anticounterfeiting based on the phosphor is not only safer but also more convenient in application.

Identification of a novel collagen-like peptide by high-throughput screening for effective wound-healing therapy.

Tissue regeneration and wound healing are still serious clinical complications globally and lack satisfactory cures. Inspired by the impressive regeneration ability of the post-injury earthworms and their widely accepted medicinal properties, we screened and identified a novel collagen-like peptide from the amputated earthworms using high-throughput techniques, including transcriptomics, proteomics, and mass spectrum. The identified collagen-like peptide col4a1 was cloned and expressed to comprehensively investigate the wound healing effect and underlying mechanism. It exerted significant effects on wound healing both in vitro and in vivo, including enhanced viability, proliferation, migration of fibroblasts, granulation, and collagen deposition. Moreover, the col4a1 functioned via binding with integrin α2ß1 and upregulating the RAS/MAPK signaling pathway. This work demonstrates that the novel collagen-like peptide col4a1 obtained from the amputated earthworms enables enhanced wound healing and provides new opportunities for wound care.