Advances in prostate cancer research models:From transgenic mice to tumor xenografting models

The identification of the origin and molecular characteristics of prostate cancer(PCa)has crucial implications for personalized treatment.The development of effective treatments for PCa has been limited;however,the recent establishment of several transgenicmouse lines and/or xenografting models is better reflecting the disease in vivo.With appropriate models,valuable tools for elucidating the functions of specific genes have gone deep into prostate development and carcinogenesis.In the present review,we summarize a number of important PCa research models established in our laboratories(PSA-Cre-ERT2/PTEN transgenic mouse models,AP-OX model,tissue recombination-xenografting models and PDX models),which represent advances of translational models from transgenic mouse lines to human tumor xenografting.Better understanding of the developments of these models will offer new insights into tumor progression and may help explain the functional significance of genetic variations in PCa.Additionally,this understanding could lead to new modes for curing PCa based on their particular biological phenotypes.

Transfer RNA-derived fragment tRF-23-Q99P9P9NDD promotes progression of gastric cancer by targeting ACADSB

Gastric cancer(GC)is one of the most common gastrointestinal tumors.As a newly discovered type of non-coding RNAs,transfer RNA(tRNA)-derived small RNAs(tsRNAs)play a dual biological role in cancer.Our previous studies have demonstrated the potential of tRF-23-Q99P9P9NDD as a diagnostic and prognostic biomarker for GC.In this work,we confirmed for the first time that tRF-23-Q99P9P9NDD can promote the proliferation,migration,and invasion of GC cells in vitro.The dual luciferase reporter gene assay confirmed that tRF-23-Q99P9P9NDD could bind to the 3'untranslated region(UTR)site of acyl-coenzyme A dehydrogenase short/branched chain(ACADSB).In addition,ACADSB could rescue the effect of tRF-23-Q99P9P9NDD on GC cells.Next,we used Gene Ontology(GO),the Kyoto Encyclopedia of Genes and Genomes(KEGG),and Gene Set Enrichment Analysis(GSEA)to find that downregulated ACADSB in GC may promote lipid accumulation by inhibiting fatty acid catabolism and ferroptosis.Finally,we verified the correlation between ACADSB and 12 ferroptosis genes at the transcriptional level,as well as the changes in reactive oxygen species(ROS)levels by flow cytometry.In summary,this study proposes that tRF-23-Q99P9P9NDD may affect GC lipid metabolism and ferroptosis by targeting ACADSB,thereby promoting GC progression.It provides a theoretical basis for the diagnostic and prognostic monitoring value of GC and opens upnew possibilities for treatment.

Multiple regulatory roles of the transfer RNA-derived small RNAs in cancers

With the development of sequencing technology,transfer RNA(tRNA)-derived small RNAs(tsRNAs)have received extensive attention as a new type of small noncoding RNAs.Based on the differences in the cleavage sites of nucleases on tRNAs,tsRNAs can be divided into two categories,tRNA halves(tiRNAs)and tRNA-derived fragments(tRFs),each with specific subcellular localizations.Additionally,the biogenesis of tsRNAs is tissue-specific and can be regulated by tRNA modifications.In this review,we first elaborated on the classification and biogenesis of tsRNAs.After summarizing the latest mechanisms of tsRNAs,including transcriptional gene silencing,post-transcriptional gene silencing,nascent RNA silencing,translation regulation,rRNA regulation,and reverse transcription regulation,we explored the representative biological functions of tsRNAs in tumors.Furthermore,this review summarized the clinical value of tsRNAs in cancers,thus providing theoretical support for their potential as novel biomarkers and therapeutic targets.

Injectable hydrogels for spinal cord injury repair

Spinal cord injury(SCI)often causes severe functional impairment of body,which leads to a huge burden to the patient and the whole society.Many strategies,especially biomaterials,have been employed for SCI repair.Among various biomaterials,injectable hydrogels have attracted much attention because of their ability to load functional components and be injected into the lesioned area without surgeries.In this review,we summarize the recent progress in injectable hydrogels for SCI repair.We firstly introduce the pathophysiology of SCI,which reveals the mechanism of clinical manifestations and determines the therapeutic schedule.Then,we describe the original sources of polymers and the crosslinking manners in forming hydrogels.After that,we focus on the in vivo therapeutic strategies and effects of injectable hydrogels.Finally,the recent challenges and future outlook of injectable hydrogel for SCI repair are concluded and discussed.We believe this review can be helpful and inspire the further development of injectable hydrogels for SCI repair.