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| 1 | HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation显示文摘N6-methyladenosine(m6A),and its reader protein YTHDF1,play a pivotal role in human tumorigenesis by affecting nearly everystage of RNA metabolism.Autophagy activation is one of the ways by which cancer cells survive hypoxia.However,the possibleinvolvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma(HCO).In this study,specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing,knockout,and-knockdownHCC cells,HCC organoids,and HCC patient-derived xenograft(PDX)murine models.YTHDF1 expression and hypoxia inducedautophagy were significantly correlated in vitro;signifhcant overexpression of YTHDF1 in HCC tissues was associated with poorprognosis,Multivariate cox regression analysis identihed YTHDF1 expression as an independent prognostic factor in patients withHCC.Multiple HC models conhrmed that YTHDF1 deficiency inhibited HCC autophagy,growth,and metastasis.Luciferase reporterassays and chromatin immunoprecipitation demonstrated that HlIF-1a regulated YTHDF1 transcription by directly binding to itspromoter region under hypoxia.The results of methylated RNA immunoprecipitation sequencing,proteomics,and polysomeprofling indicated that YTHDF1 contibuted to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modifhed ATG2A and ATG14 mRNA,thus facilitating autophagy and autophagy-related malignancy of HCC.Taken together,HlE-1d-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent manner.Our fndings suggest thatYTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC. | Qing Li Yong Ni Liren Zhang Runqiu Jiang Jing Xu Hong Yang Yuanchang Hu Jiannan Qiu Liyong Pu Jinhai Tang Xuehao Wang | 2021 | Signal Transduction and Targeted Therapy2021，6，3： | 24 |
| 2 | Sox31 is involved in central nervous system anteroposterior regionalization through regulating the organizer activity in zebrafish显示文摘短袜总科蛋白质是包含高度保存的高活动性的组(HMG ) 的因素关并且参加的 DNA 有约束力的 transcriptional 各种各样的开发过程。Sox31 是在卵母细胞供应的一个母亲的因素并且在中间胞胚的转变(MBT ) 期间开始它的 zygotic 表示。从 gastrulation 舞台,它主要居住在神经织物。宫外地, Sox31 mRNA 的表示导致 cyclopia,熔化眼睛,或完全前面的头结构的损失,在里面与严重脊索缺点伴随。当以后的神经织物先前地膨胀时,分子的标记显示织物严厉地减少的那前脑。另外,组织者说明也被压制。相对地, antisense morpholino 典型地设计了机能上地击倒的 Sox31 原因 dorsalized 显型和颠倒的中央神经系统(CNS ) anteroposterior (AP ) patterning。在 Sox31 HMG DNA 有约束力的领域被熔化到抄写激活域(VP16 ) 或抄写抑制领域(EnR ) 的地方,有妄想的构造的功能的获得建议 Sox31 在 vivo 充当 transcriptional suppressor。Bozozok (法) 的表示, pre-MBT Wnt/-catenin 信号的直接目标基因,被 Sox31 压制。因此,揭开在 Sox31 和 -catenin-related transcriptional 活动之间的关系,我们在 HEK293T 房间设计了顶 / 蠢人的酶试金,并且发现没有影响 -catenin 的稳定性, Sox31 能确实压制 Tcf/Lef-dependent transcriptional 活动。而且, post-MBT Wnt 信号在相应于压制的脑的最后部结构的 Sox31 morphants 被减少,当过多的 Sox31 引起的 phenotypic 缺点能被 Wnt 对手 dkk1 救时。一起拿, Sox31 作为一个必要 CNS AP patterning 决定因素工作并且与组织者说明协调 CNS AP patterning 进程。 | Shengnan Hu Zhili Wu Yuanchang Yan Yiping Li | 2011 | Acta Biochimica et Biophysica Sinica2011，43，5： | 2 |
| 3 | Differential response of multiple zebrafish hepatic F-box protein genes to 17α-ethinylestradiol treatment显示文摘Estrogens are accumulating in environment and their effects on a variety of reproductive processes and tumorigenesis were reported by previous study, but the mechanism of estrogen promoting neoplasia was still not clear. F-box protein (FBP) is the component of E3 ubiquitin ligase which takes part in a variety of key biological processes. In this study, using mature male zebrafish, which are more sensitive to estrogen treatment, we examined influence of 17α-ethinylestradiol (EE2) exposure on the expression of a series of hepatic FBP genes, which take part in a variety of biological processes, including tumorigenesis. The influence of EE2 on the expression of hepatic mRNA concentrations of FBP genes were quantified based on the expression of the optimal internal control gene in male zebrafish after 7-day exposure to EE2, from a low-dose concentration (1 ng/L) to environmentally relevant concentrations (10, 100 ng/L). Our results showed that EE2 exposure reduced the expression of fbxl14a, fbxl14b, fbxo25 and β-TRCP2b, but enchanced the expression of skp2. While the alterations in fbxl2, fbxw7, fbxo9, β-TRCP2a, fbxl18 and fbxo45 mRNA levels were not observed after EE2 exposure. Thus, our results showed that the expression of hepatic FBP genes exhibited differentially in male zebrafish exposed EE2. The changes of the expression level of FBP genes induced by EE2 may be an important clue to elucidate the correlations of estrogen and hepatic tumors. | Hongping Zheng Shifeng Li Zhili Wu Yunbin Zhang Shengnan Hu Yuanchang Yan Yiping Li | 2011 | Journal of Environmental Sciences2011，23，4： | 2 |
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