ARNTL inhibits the malignant behaviors of oral cancer by regulating autophagy in an AKT/mTOR pathway-dependent manner

作者全名："Chen, KuiChi; Li, HanXue; Li, YueHeng; Yang, ZhengYan; Luo, Jun; Zhou, Zhi"

作者地址："[Chen, KuiChi; Li, HanXue] Chongqing Key Lab Oral Dis & Biomed Sci, Chongqing, Peoples R China; [Chen, KuiChi; Li, HanXue] Chongqing Municipal Key Lab Oral Biomed Engn Highe, Chongqing, Peoples R China; [Li, HanXue; Li, YueHeng; Yang, ZhengYan; Luo, Jun; Zhou, Zhi] Chongqing Med Univ, Stomatol Hosp, 5 Shangqingsi Rd, Chongqing 400015, Peoples R China"

通信作者："Luo, J; Zhou, Z (通讯作者)，Chongqing Med Univ, Stomatol Hosp, 5 Shangqingsi Rd, Chongqing 400015, Peoples R China."

来源：CANCER SCIENCE

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001046000000001

JCR分区：Q1

影响因子：4.5

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：ARNTL; autophagy; carcinogenesis; oral cancer; tumor suppressor

摘要："Current studies have shown that ARNTL, an important clock gene, plays an anticancer role and is downregulated in certain types of cancer. However, the biological functions and mechanisms of ARNTL in tumors remain largely unknown. This study aimed to elucidate how ARNTL-induced autophagy impacts the biological properties of tongue squamous cell carcinoma (TSCC) cells and the mechanisms by which ARNTL expression activates autophagy. ARNTL was stably overexpressed in TSCC cells to investigate its functions in vitro and in vivo. We found that activation of autophagy induced by ARNTL decreases cell proliferation, enhances cell death, and hinders the migratory ability of TSCC cells. Moreover, ARNTL antagonizes the AKT/mTOR pathway, which potentiates autophagy induction. The manipulation of Akt activation cancels the effects of ARNTL overexpression on the biological behaviors of TSCC cells. Furthermore, after the addition of SC79, the upregulated BAX expression due to ARNTL overexpression and downregulated expressions of BCL-2 and MMP2 were remarkably rescued. In vivo tumorigenicity assays and immunohistochemistry also confirmed that ARNTL overexpression suppresses tumor development. Our study found for the first time that ARNTL inhibits the malignant behaviors of oral cancer cells by regulating autophagy in an AKT/mTOR pathway-dependent manner, which provides a novel theoretical basis for the potential future application of ARNTL to treat patients with oral cancer."

基金机构：Natural Science Foundation Project of Chongqing [CSTC2019jcyj-msxmX0191]; Science Project of the Chongqing Municipal Health Commission. The First batch of key Disciplines On Public Health in Chongqing [2021MSXM31]

基金资助正文："Natural Science Foundation Project of Chongqing, Grant/Award Number: CSTC2019jcyj-msxmX0191; Science Project of the Chongqing Municipal Health Commission. The First batch of key Disciplines On Public Health in Chongqing, Grant/Award Number: 2021MSXM31"