Identification of CCI-38 as an effective YTHDF2 inhibitor 识别CCI-38作为有效的YTHDF2抑制剂 Para_01 我们接下来进行了基于结构的虚拟筛选,并发现79种化合物与YTHDF2的RNA结合域具有较高的对接评分(但不包括YTHDC1或METTL3)(图6G和6H)。 其中,我们发现#38(NSC-639513,以下简称CCI-38)、#63(NSC-126269...
肿瘤细胞分泌的丝氨酸蛋白酶抑制剂E2(serpin peptidase inhibitor clade E member 2,SERPINE2)通过重新编程肿瘤脉管系统赋予肿瘤侵袭性和转移性过程[57],YTHDF2在肝癌[21]中过表达降低了肿瘤血管密度和通透性,并通过靶向SERPINE2来抵抗肿瘤血管生成或血管拟态,从而抑制肿瘤转移。核因子κB(nuclear factor κB,NF-κB...
Despite tumor-associated macrophages (TAMs) playing a key role in shaping the tumor microenvironment (TME), the mechanisms by which TAMs influence the TME and contribute to cancer progression remain unclear. Here, we show that the N6-methyladenosine read
Matrilin-3 overexpression downregulated p-PI3K/PI3K, p-AKT/AKT, ZO-1, VE-cadherin and occludin, and upregulated p-JNK/JNK in ischemic rat brains; these effects were reversed by LY294002 (a PI3K inhibitor). YTHDF2 knockdown inactivated the PI3K/AKT pathway, inhibited inflammation and ...
Clinically, the stability of hypoxia-inducible factor (HIF) is linked to poor survival in various cancers [97,98]. It has been reported that the activity of the YTHDF2 promoter could be reduced in hypoxia and reversed by the application of a HIF-2α inhibitor, which indicated the relationsh...
and italone can cause B-ALLd YTHDF2 enhances ATP synthesis by targeting ATP5PB/ATP5MG/ATP5MF as an RNA m 5 C readerd YTHDF2 destabilizes CD19/HLA-DMA/B and promotesimmune evasion as an RNA m 6 A readerd YTHDF2 inhibitor CCI-38 suppresses B cell malignanciesand sensitizes them to...
Clinically, the stability of hypoxia-inducible factor (HIF) is linked to poor survival in various cancers [97,98]. It has been reported that the activity of the YTHDF2 promoter could be reduced in hypoxia and reversed by the application of a HIF-2α inhibitor, which indicated the relationsh...
(Fig.7A). However, knockdown of either miR-378 or miR-378-5P using specific miRNA inhibitor resulted in a significant suppression of myotube formation during myogenic differentiation (Fig.7B-D). Consistently, depletion of miR-378 or miR-378-5p resulted in significant decreases in both the ...
2C). Decreased expression of Cyclin B1, a marker of G2/M phase, and increased p21 expression, a cell-cycle inhibitor, were observed in cells with YTHDF2 knockdown (Supplementary Fig. S2C). Similarly, in contrast to the control group, deletion of YTHDF2 facilitated cell apoptosis in DLBCL...
Interestingly, introducing HCC cells to hypoxia enabled this epitranscriptomic transformation in vitro, affecting common oncogenes such as those involved in ‘serine-type endopeptidase inhibitor activity’. Putatively, the ‘hyper-up’ feature is caused, at least in part, by hypoxia-induced YTHDF2 ...