Ferroptosis:a critical mechanism of N^(6)-methyladenosine modification involved in carcinogenesis and tumor progression

Ferroptosis is an iron-dependent regulatory cell necrosis induced by iron overload and lipid peroxidation.It occurs when multiple redoxactive enzymes are ectopically expressed or show abnormal function.Hence,the precise regulation of ferroptosis-related molecules is mediated across multiple levels,including transcriptional,posttranscriptional,translational,and epigenetic levels.N^(6)-methyladenosine(m^(6)A)is a highly evolutionarily conserved epigenetic modification in mammals.The m^(6)A modification is commonly linked to tumor proliferation,progression,and therapy resistance because it is involved in RNA metabolic processes.Intriguingly,accumulating evidence suggests that dysregulated ferroptosis caused by the m^(6)A modification drives tumor development.In this review,we summarized the roles of m^(6)A regulators in ferroptosis-mediated malignant tumor progression and outlined the m^(6)A regulatory mechanism involved in ferroptosis pathways.We also analyzed the potential value and application strategies of targeting m^(6)A/ferroptosis pathway in the clinical diagnosis and therapy of tumors.

Expression pattern and regulation of head-to-head genes Vps36 and Ckap2 during chicken follicle development

Vacuolar protein sorting 36(VPS36),a protein primarily known for its role in the Endosomal Sorting Complex Required for Transport pathway,has recently been shown to be linked to chicken reproduction.Previous research showed that Vps36 is significantly downregulated in sexually mature chicken ovaries compared to immature ones.In this study,using real-time quantitative RT-PCR,we investigated the expression pattern of Vps36 and its head-to-head gene Ckap2 mRNA in chicken follicles.Small white follicles were found to have significantly higher expression of Vps36 and Ckap2 mRNA than any other sized follicles(P<0.05).The expression of Vps36 and Ckap2 mRNA were detected in both granulosa and theca layers of pre-ovulatory follicles,the expression of Ckap2 in theca layers was slightly higher than in granulosa cells.Treatment of small yellow follicles with folliclestimulating hormone and estradiol resulted in a marked decrease of both Vps36 and Ckap2 mRNA(P<0.05);however,progesterone,transforming growth factor-β1 and luteinizing hormone induced no significant changes in Vps36 and Ckap2 mRNA expression in these follicles.These results indicate that the head-to-head genes of Vps36 and Ckap2 exhibit similar expression in chicken follicles and are involved in chicken follicle development.

Pluripotent stem cells secrete Activin A to improve their epiblast competency after injection into recipient embryos

It is not fully clear why there is a higher contribution of pluripotent stem cells （PSCs） to the chimera produced by injection of PSCs into 4-cell or 8-cell stage embryos compared with blastocyst injection. Here, we show that not only embryonic stem cells （ESCs） but also induced pluripotent stem cells （iPSCs） can generate F0 nearly 100% donor cell-derived mice by 4-cell stage embryo injection, and the approach has a ＂dose effect＂. Through an analysis of the PSC-secreted proteins, Activin A was found to impede epiblast （EPI） lineage development while promoting trophectoderm （TE） differentiation, resulting in replacement of the EPI lineage of host embryos with PSCs. Interestingly, the injection of ESCs into blastocysts cultured with Activin A （cultured from 4-cell stage to early blastocyst at E3.5） could increase the contribution of ESCs to the chimera. The results indicated that PSCs secrete protein Activin A to improvetheir EPI competency after injection into recipient embryos through influencing the development of mouse early embryos. This result is useful for optimizing the chimera production system and for a deep understand- ing of PSCs effects on early embryo development.