Hypoxia induced cell dormancy of salivary adenoid cystic carcinoma through miR-922/DEC2 axis.
Hypoxia induced cell dormancy of salivary adenoid cystic carcinoma through miR-922/DEC2 axis.
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DOI：
10.1016/j.tranon.2023.101868
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发表时间：
2024-02
影响因子：
5
通讯作者：
Tang, Ya-ling
中科院分区：
文献类型：
--
作者：
Dai, Li;Xian, Hongchun;Wang, Haofan;Li, Mao;Zhang, Mei;Liang, Xin-hua;Tang, Ya-ling
miR-922在SACC中作为DmiR， miR-922/DEC2轴激活SACC细胞休眠，促进脂质代谢重编程。缺氧通过HIF1a/miR-922/DEC2反馈回路诱导SACC细胞休眠。过表达miR-922可提高CPT1A水平，但降低DGAT1、DGAT2和ACAT1水平；抑制miR-922可降低CPT1A水平，但升高DGAT1、DGAT2和ACAT1水平。研究表明，缺氧可使癌细胞处于休眠状态，同时这些细胞倾向于扩散并最终导致转移。然而，分子机制仍然是难以捉摸的。目的探讨休眠相关的microRNAs （DmiRs）是否参与缺氧诱导的唾液腺样囊性癌（SACC）细胞休眠。本研究在前期研究DEC2过表达诱导SACC细胞休眠的基础上，基于临床样本、体外2D和3D模型以及裸鼠体内模型，多角度探讨了miR-922/DEC2对SACC的生物学效应。根据已有的SACC组织microRNA阵列，我们发现miR-922在SACC组织中表达上调，且与DEC2呈负相关，提示miR-922可能作为DmiR参与SACC细胞休眠的激活。然后，我们发现miR-922低SACC细胞表现出细胞休眠和低水平的脂肪酸氧化，并倾向于通过DEC2积累脂滴。此外，HIF1a下调miR-922水平诱导SACC细胞休眠。此外，在裸鼠异种移植物中，miR-922的抑制作用减弱了原发肿瘤的生长和SACC的肺转移。miR-922/DEC2轴是缺氧诱导的细胞休眠所必需的，在SACC脂质代谢重编程中发挥重要作用。
miR-922 performed as a DmiR in SACC and miR-922/DEC2 axis activated SACC cell dormancy and promoted lipid metabolism reprogramming. Hypoxia induced SACC cell dormancy via HIF1a/miR-922/DEC2 feedback loop. The overexpression of miR-922 promoted the level of CPT1A but decreased that of DGAT1, DGAT2 and ACAT1 while the inhibition of miR-922 lowered the level of CPT1A but increased that of DGAT1, DGAT2 and ACAT1. Hypoxia has been shown to induce cancer cells to become dormant meanwhile these cells inclined to disseminate and eventually cause metastasis. However, the molecular mechanism is still elusive. The purpose is to explore whether dormancy-associated microRNAs (DmiRs) get involved in hypoxia-induced cell dormancy of salivary adenoid cystic carcinoma (SACC). This study performed multi-perspective investigation of the biological effects of miR-922/DEC2 on SACC based on clinical samples, 2D and 3D in vitro model and nude mice in vivo model, based on our previous study of overexpression of DEC2 inducing SACC cellular dormancy. According to the existing microRNA array of SACC tissue, we found that miR-922 was upregulated in SACC tissue and was inversely correlated with DEC2, suggesting that miR-922 might participate in the activation of SACC cell dormancy as a DmiR. Then, we found miR-922 low SACC cells exhibited cell dormancy and a low level of fatty acid oxidation with propensity for lipid droplets accumulation through DEC2. Moreover, HIF1a downregulated the level of miR-922 to induce SACC cell dormancy. In addition, in xenografts of nude mice the inhibition of miR-922 attenuated the growth of primary tumor and the lung metastasis of SACC. miR-922/DEC2 axis was necessary to hypoxia-induced cell dormancy and played an important role in the lipid metabolism reprogramming of SACC.
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DOI：
10.1186/s13046-021-01956-0
发表时间：
2021-05-14
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Yang X;Wu JS;Li M;Zhang WL;Gao XL;Wang HF;Yu XH;Pang X;Zhang M;Liang XH;Tang YL
通讯作者：
Tang YL
影响因子：
11.2
作者：
Barkan D;Kleinman H;Simmons JL;Asmussen H;Kamaraju AK;Hoenorhoff MJ;Liu ZY;Costes SV;Cho EH;Lockett S;Khanna C;Chambers AF;Green JE
通讯作者：
Green JE
DOI：
10.1038/s41580-021-00354-w
发表时间：
2021-06
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Agbu P;Carthew RW
通讯作者：
Carthew RW
影响因子：
4.7
作者：
Di Villeneuve L;Souza IL;Tolentino FDS;Ferrarotto R;Schvartsman G
通讯作者：
Schvartsman G
DOI：
10.4161/trns.25558
发表时间：
2013-07
期刊：
Transcription
影响因子：
--
作者：
Almog N;Briggs C;Beheshti A;Ma L;Wilkie KP;Rietman E;Hlatky L
通讯作者：
Hlatky L