Inorganic arsenic exposure promotes malignant progression by HDAC6-mediated down-regulation of HTRA1

作者全名："Chen, Jiafeng; Lei, Cece; Nie, Daibang; Ge, Huan; Li, Jian; Lei, Changbin; Wang, Wang"

作者地址："[Chen, Jiafeng; Lei, Cece; Nie, Daibang; Wang, Wang] Chongqing Med Univ, Coll Basic Med, Dept Immunol, Chongqing, Peoples R China; [Chen, Jiafeng; Lei, Cece; Nie, Daibang; Wang, Wang] Chongqing Med Univ, Chongqing Key Lab Basic & Translat Res Tumor Immun, Chongqing, Peoples R China; [Ge, Huan; Li, Jian; Lei, Changbin] Xiangnan Univ, Dept Orthoped, Affiliated Hosp, Chenzhou, Peoples R China; [Lei, Changbin] Heavy Met Pollut & Canc Prevent Technol Res Ctr, Chenzhou, Peoples R China; [Lei, Changbin] Xiangnan Univ, Dept Orthoped, Affiliated Hosp, Chenzhou, Peoples R China; [Lei, Changbin] Heavy Met Pollut & Canc Prevent Technol Res Ctr, 25 Renmin West Rd, Chenzhou 42300, Hunan, Peoples R China; [Wang, Wang] Chongqing Med Univ, Coll Basic Med, Dept Immunol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China"

通信作者："Lei, CB (通讯作者)，Xiangnan Univ, Dept Orthoped, Affiliated Hosp, Chenzhou, Peoples R China.; Lei, CB (通讯作者)，Heavy Met Pollut & Canc Prevent Technol Res Ctr, 25 Renmin West Rd, Chenzhou 42300, Hunan, Peoples R China.; Wang, W (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Immunol, 1 Yixueyuan Rd, Chongqing 400016, Peoples R China."

来源：JOURNAL OF APPLIED TOXICOLOGY

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000947000900001

JCR分区：Q3

影响因子：2.7

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：cancer; HDAC6; HTRA1; inorganic arsenic; intestine

摘要："Inorganic arsenic (iAs) has been a human health concern and is associated with intestinal malignancies. However, the molecular mechanisms of the iAs-induced oncogenic process in intestine epithelial cells remain elusive, partly because of the known hormesis effect of arsenic. Here, we established that six-month exposure to iAs at a concentration similar to those found in contaminated drinking water could promote malignant characteristics, including enhanced proliferation and migration, resistance to apoptosis, and mesenchymal-like transition in Caco-2 cells. Transcriptome analysis and mechanism study revealed that key genes and pathways involved in cell adhesion, inflammation and oncogenic regulation were altered during chronic iAs exposure. Specifically, we uncovered that down-regulation of HTRA1 was essential for the iAs-induced acquisition of the cancer hallmarks. Further, we evidenced that the loss of HTRA1 during iAs-exposure could be restored by HDAC6 inhibition. Caco-2 cells with chronic exposure to iAs exhibited enhanced sensitivity to WT-161, a specific inhibitor of HDAC6, when used alone than in combination with a chemotherapeutic agent. These findings provide valuable information for understanding the mechanisms of arsenic-induced carcinogenesis and facilitating the health management of populations in arsenic-polluted areas."

基金机构：Chenzhou Science and Technology Bureau

基金资助正文：This work was supported in part by the Chenzhou Science and Technology Bureau