Doxycycline hydrochloride inhibits the progress of malignant rhabdoid tumor of kidney by targeting MMP17 and MMP1 through PI3K-Akt signaling pathway

作者全名："Mi, Tao; Zhang, Zhaoxia; Zhanghuang, Chenghao; Jin, Liming; Tan, Xiaojun; Liu, Jiayan; Wu, Xin; Li, Mujie; Wang, Jinkui; Wang, Zhang; Guo, Peng; He, Dawei"

作者地址："[Mi, Tao; Zhang, Zhaoxia; Zhanghuang, Chenghao; Jin, Liming; Tan, Xiaojun; Liu, Jiayan; Wu, Xin; Li, Mujie; Wang, Jinkui; Wang, Zhang; Guo, Peng; He, Dawei] Chongqing Key Lab, Children Urogenital Dev & Tissue Engn, Chongqing 400014, Peoples R China; [Mi, Tao; Zhang, Zhaoxia; Zhanghuang, Chenghao; Jin, Liming; Tan, Xiaojun; Liu, Jiayan; Wu, Xin; Li, Mujie; Wang, Jinkui; Wang, Zhang; Guo, Peng; He, Dawei] Chongqing Med Univ, Chongqing Key Lab Pediat, Childrens Hosp, Chongqing 400014, Peoples R China; [He, Dawei] Chongqing Med Univ, Childrens Hosp, Dept Urol, Chongqing 400014, Peoples R China; [He, Dawei] Chongqing Med Univ, Affiliated Childrens Hosp, Key Lab Childrens Dev Dis Res, Minist Educ, Chongqing 400014, Peoples R China; [He, Dawei] Chongqing Med Univ, Children 's Hosp Affiliated, Natl Int Sci & Technol Cooperat Base Major Childho, Chongqing 400014, Peoples R China; [He, Dawei] Chongqing Med Univ, Childrens Hosp Affiliated, Natl Clin Res Ctr Child Hlth & Dis, Chongqing 400014, Peoples R China; [Guo, Peng] Chinese Acad Sci, Inst Basic Med & Canc IBMC, Hangzhou 310022, Zhejiang, Peoples R China; [He, Dawei] Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China"

通信作者："He, DW (通讯作者)，Chongqing Med Univ, Dept Urol, Childrens Hosp, Chongqing 400014, Peoples R China."

来源：EUROPEAN JOURNAL OF PHARMACOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:001153801300001

JCR分区：Q1

影响因子：5

年份：2024

卷号：964

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Malignant rhabdoid tumor of kidney; MMP17; MMP1; Doxycycline hydrochloride; Machine learning

摘要："Objective: To identify therapeutic targets for malignant rhabdoid tumors of kidney (MRTK) and to investigate the effects and underlying mechanism of doxycycline hydrochloride on these tumors. Methods: Gene expression and clinical data of MRTK were retrieved from the TARGET database. Differentially expressed genes (DEGs) and prognostic-related genes (PRGs) were selected through a combination of statistical analyses. The functional roles of MMP17 and MMP1 were elucidated through RNA overexpression and intervention experiments. Furthermore, in vitro and in vivo studies provided evidence for the inhibitory effect of doxycycline hydrochloride on MRTK. Additionally, transcriptome sequencing was employed to investigate the underlying molecular mechanisms. Results: 3507 DEGs and 690 PRGs in MRTK were identified. Among these, we focused on 41 highly expressed genes associated with poor prognosis and revealed their involvement in extracellular matrix regulatory pathways. Notably, MMP17 and MMP1 stood out as particularly influential genes. When these genes were knocked out, a significant inhibition of proliferation, invasion and migration was observed in G401 cells. Furthermore, our study explored the impact of the matrix metalloproteinase inhibitor, doxycycline hydrochloride, on the malignant progression of G401 both in vitro and in vivo. Combined with sequencing data, the results indicated that doxycycline hydrochloride effectively inhibited MRTK progression, due to its ability to suppress the expression of MMP17 and MMP1 through the PI3K-Akt signaling pathway. Conclusion: Doxycycline hydrochloride inhibits the expression of MMP17 and MMP1 through the PI3K-Akt signaling pathway, thereby inhibiting the malignant progression of MRTK in vivo and in vitro."

基金机构：Project of Science and Technol- ogy Commission of Chongqing [7000025]; Chongqing Province Science and Technology Innovation and Application Demonstration Project [cstc2019jscx-tjsbX0003]

基金资助正文：<BOLD>Funding</BOLD> This research was supported by the Project of Science and Technol- ogy Commission of Chongqing (No. 7000025) and Chongqing Province Science and Technology Innovation and Application Demonstration Project (cstc2019jscx-tjsbX0003) .