"Exosomal miR-211-5p regulates glucose metabolism, pyroptosis, and immune microenvironment of melanoma through GNA15"

作者全名："Zeng, Bin; Chen, Yuting; Chen, Hao; Zhao, Qiting; Sun, Zhiwei; Liu, Doudou; Li, Xiaoshuang; Zhang, Yuhan; Wang, Jianyu; Xing, H. Rosie"

作者地址："[Zeng, Bin; Zhao, Qiting; Sun, Zhiwei; Wang, Jianyu] Chongqing Med Univ, Inst Life Sci, Chongqing 400016, Peoples R China; [Chen, Yuting; Chen, Hao; Liu, Doudou; Li, Xiaoshuang; Zhang, Yuhan; Xing, H. Rosie] Chongqing Med Univ, Coll Biomed Engn, State Key Lab Ultrasound Med & Engn, Chongqing 400016, Peoples R China; [Wang, Jianyu; Xing, H. Rosie] Yi Xue Yuan Rd, Chongqing 400016, Peoples R China"

通信作者："Wang, JY; Xing, HR (通讯作者)，Yi Xue Yuan Rd, Chongqing 400016, Peoples R China."

来源：PHARMACOLOGICAL RESEARCH

ESI学科分类：PHARMACOLOGY & TOXICOLOGY

WOS号：WOS:000926969500001

JCR分区：Q1

影响因子：9.3

年份：2023

卷号：188

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：Exosome; miRNA-211-5p; Glycolysis; Pyroptosis; GNA15; ZFYVE26

摘要："Despite the unprecedented advancement of cancer treatment, the prognosis for patients with metastatic stage of cancer remains poor. The challenge that underlines this clinical dilemma is the complexity of metastasis. The conventional experiment-driven discovery approaches (the ""wet lab"") yield overly simplified one-to-one mech-anistic relationships that are inept of elucidating the complexity of metastasis. Metastasis research also suffers from the knowledge and skill deficiency of the individual investigators. The importance of the present study is the demonstration that the ""dry-lab-driven discovery and wet-lab validation"" approach can improve the effi-ciency of studying complex biological behaviors, and can yield more reliable, objective and comprehensive mechanistic findings that are have clinical significance. Specifically, we applied this approach to study the mechanisms that underline the involvement of exosomal miRNAs in transferring the metastatic capability be-tween heterogenous melanoma cancer cells. We show that the highly metastatic melanoma tumor cells (POL) can transfer their metastatic competency to the low-metastatic melanoma tumor cells (OL) by exosomal miR-211-5p. The oncogenic activity of miR-211-5p is mediated by the target gene guanine nucleotide-binding protein subunit alpha-15 (GNA15) through modifying the immune function of the tumor microenvironment extrinsically; as well as through inhibiting pyroptosis and augmenting glycolysis within OL cells intrinsically. In addition, we show that exosomal sorting of miR-211-5p is like selective and is subjected to regulation by a transcriptional feedback loop between miR-211-5p and zinc finger FYVE-type containing 26 (ZFYVE26). Furthermore, the ""8-genes pyroptosis Risk model"" derived from LASSO regression analysis was verified as an independent prognostic factor for melanoma."

基金机构："National Natural Science Foundation of China [82073277, 82173247]; Science and Technology Project, Education Department of Chongqing [KJQN202100404]; Science and Technology Project of Chongqing Yuzhong District [20200110]; Project of Chongqing Key Laboratory of Human Embryo Engineering & Chongqing Health Center for Women and Children [2020KFKT003]"

基金资助正文："This work was supported by the National Natural Science Foundation of China (Grant nos. 82073277 and 82173247), the Science and Technology Project Affiliated to the Education Department of Chongqing (Grant no. KJQN202100404), Science and Technology Project of Chongqing Yuzhong District (Grant no. 20200110) and the Project of Chongqing Key Laboratory of Human Embryo Engineering & Chongqing Health Center for Women and Children (Grant no. 2020KFKT003)."