Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway.
Silencing DTX3L Inhibits the Progression of Cervical Carcinoma by Regulating PI3K/AKT/mTOR Signaling Pathway.
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DOI：
10.3390/ijms24010861
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发表时间：
2023-01-03
影响因子：
5.6
通讯作者：
Yang, Chunhua
中科院分区：
文献类型：
--
作者：
Hu, Wei;Hu, Yaorui;Pei, Yao;Li, Rongrong;Xu, Fuyi;Chi, Xiaodong;Mi, Jia;Bergquist, Jonas;Lu, Lu;Zhang, Luping;Yang, Chunhua
关键词：
宫颈癌（CC）是世界上第二大流行的女性妇科癌症。为了更好地了解CC发展的机制，对8名患者的CC和邻近正常组织进行了高分辨率无标签质谱分析。共鉴定出2631个蛋白，其中46个显著差异表达蛋白（DEPs）在CC与正常组织中存在差异（p < 0.01， fold change bbb10或<0.1）。匠心通路分析显示，大多数蛋白参与eIF4和p70S6K信号和mTOR信号的调控。46个DEPs中，与邻近正常组织相比，CC组织中Integrinβ6 （ITGB6）、PPP1CB、TMPO、PTGES3 （P23）和DTX3L显著上调，Desmin （DES）显著下调。在体内和体外实验中，敲低DTX3L可抑制CC细胞的增殖、迁移、侵袭和异种移植瘤发生，并增强细胞凋亡。与单用顺铂治疗相比，沉默DTX3L联合顺铂治疗可诱导更高的细胞凋亡百分比。此外，DTX3L沉默抑制PI3K/AKT/mTOR信号通路。因此，我们的研究结果表明DTX3L可以通过PI3K/AKT/mTOR信号通路调节CC的进展，可能是CC的一种新的生物标志物和治疗靶点。
Cervical carcinoma (CC) is the second most prevalent gynecologic cancer in females across the world. To obtain a better understanding of the mechanisms underlying the development of CC, high-resolution label-free mass spectrometry was performed on CC and adjacent normal tissues from eight patients. A total of 2631 proteins were identified, and 46 significant differently expressed proteins (DEPs) were found between CC and normal tissues (p < 0.01, fold change >10 or <0.1). Ingenuity pathway analysis revealed that the majority of the proteins were involved in the regulation of eIF4 and p70S6K signaling and mTOR signaling. Among 46 DEPs, Integrinβ6 (ITGB6), PPP1CB, TMPO, PTGES3 (P23) and DTX3L were significantly upregulated, while Desmin (DES) was significantly downregulated in CC tissues compared with the adjacent normal tissues. In in vivo and in vitro experiments, DTX3L knockdown suppressed CC cell proliferation, migration, invasion and xenograft tumorigenesis, and enhanced cell apoptosis. Combination of silencing DTX3L and cisplatin treatment induced higher apoptosis percentage compared to cisplatin treatment alone. Moreover, DTX3L silencing inhibited the PI3K/AKT/mTOR signal pathway. Thus, our results suggested DTX3L could regulate CC progression through the PI3K/AKT/mTOR signal pathway and is potentially a novel biomarker and therapeutic target for CC.
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DOI：
10.1002/prca.202100127
发表时间：
2022-07
期刊：
Proteomics. Clinical applications
影响因子：
--
作者：
通讯作者：
--
影响因子：
5.5
作者：
Wang L;Sun X;He J;Liu Z
通讯作者：
Liu Z
影响因子：
6
作者：
Martínez-Rodríguez F;Limones-González JE;Mendoza-Almanza B;Esparza-Ibarra EL;Gallegos-Flores PI;Ayala-Luján JL;Godina-González S;Salinas E;Mendoza-Almanza G
通讯作者：
Mendoza-Almanza G
通过挖掘TCGA数据库鉴定下级神经胶质瘤中肿瘤微环境相关的基因。
影响因子：
0.9
作者：
Liang H;Huang C
通讯作者：
Huang C
影响因子：
--
作者：
Güzel C;Govorukhina NI;Wisman GBA;Stingl C;Dekker LJM;Klip HG;Hollema H;Guryev V;Horvatovich PL;van der Zee AGJ;Bischoff R;Luider TM
通讯作者：
Luider TM