CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression.
CLIC3 interacts with NAT10 to inhibit N4-acetylcytidine modification of p21 mRNA and promote bladder cancer progression.
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CLIC3与NAT10相互作用，以抑制p21 mRNA的N4-乙酰基胞苷的修饰并促进膀胱癌的进展。
DOI：
10.1038/s41419-023-06373-z
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发表时间：
2024-01-05
影响因子：
9
通讯作者：
Jiang, Guosong
中科院分区：
文献类型：
--
作者：
Shuai, Yujun;Zhang, Hui;Liu, Changhao;Wang, Junting;Jiang, Yangkai;Sun, Jiayin;Gao, Xincheng;Bo, Xiaochen;Xiao, Xingyuan;Liao, Xin;Huang, Chao;Chen, Hebing;Jiang, Guosong
染色质可及性在揭示基因表达调控网络方面具有重要作用，但其在膀胱癌中的应用尚未完全阐明。细胞内氯离子通道3（CLIC 3）蛋白与某些肿瘤的发生、发展有关，但CLIC 3在肿瘤中的具体作用机制尚不清楚。在这里，我们根据染色质可及性和TF基序，通过识别转录因子结合位点簇集区（TFCR）来筛选膀胱癌的关键基因。CLIC 3通过与TCGA数据库的染色质可及性数据的联合分析来鉴定。临床上，CLIC 3表达在膀胱癌中显著升高，并与患者生存率呈负相关。CLIC 3通过降低p21的表达促进膀胱癌细胞的增殖。CLIC 3与NAT10相互作用，抑制NAT10的功能，导致ac4C修饰下调，p21 mRNA稳定。总之，这些发现揭示了mRNA ac4C修饰的新机制，CLIC 3可能作为膀胱癌的潜在治疗靶点。
Chromatin accessibility plays important roles in revealing the regulatory networks of gene expression, while its application in bladder cancer is yet to be fully elucidated. Chloride intracellular channel 3 (CLIC3) protein has been reported to be associated with the progression of some tumors, whereas the specific mechanism of CLIC3 in tumor remains unclear. Here, we screened for key genes in bladder cancer through the identification of transcription factor binding site clustered region (TFCR) on the basis of chromatin accessibility and TF motif. CLIC3 was identified by joint profiling of chromatin accessibility data with TCGA database. Clinically, CLIC3 expression was significantly elevated in bladder cancer and was negatively correlated with patient survival. CLIC3 promoted the proliferation of bladder cancer cells by reducing p21 expression in vitro and in vivo. Mechanistically, CLIC3 interacted with NAT10 and inhibited the function of NAT10, resulting in the downregulation of ac4C modification and stability of p21 mRNA. Overall, these findings uncover an novel mechanism of mRNA ac4C modification and CLIC3 may act as a potential therapeutic target for bladder cancer.
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影响因子：
16
作者：
Arango, Daniel;Sturgill, David;Yang, Renbin;Kanai, Tapan;Bauer, Paulina;Roy, Jyoti;Wang, Ziqiu;Hosogane, Masaki;Schiffers, Sarah;Oberdoerffer, Shalini
通讯作者：
Oberdoerffer, Shalini
影响因子：
14.9
作者：
Sharma S;Langhendries JL;Watzinger P;Kötter P;Entian KD;Lafontaine DL
通讯作者：
Lafontaine DL
影响因子：
7.2
作者：
Becker, Peter B.;Workman, Jerry L.
通讯作者：
Workman, Jerry L.
影响因子：
11.8
作者：
Dozynkiewicz, Marta A.;Jamieson, Nigel B.;MacPherson, Iain;Grindlay, Joan;van den Berghe, Peter V. E.;von Thun, Anne;Morton, Jennifer P.;Gourley, Charlie;Timpson, Paul;Nixon, Colin;McKay, Colin J.;Carter, Ross;Strachan, David;Anderson, Kurt;Sansom, Owen J.;Caswell, Patrick T.;Norman, Jim C.
通讯作者：
Norman, Jim C.
影响因子：
16
作者：
Regner MJ;Wisniewska K;Garcia-Recio S;Thennavan A;Mendez-Giraldez R;Malladi VS;Hawkins G;Parker JS;Perou CM;Bae-Jump VL;Franco HL
通讯作者：
Franco HL