The Diurnal Transcriptome Reveals the Reprogramming of Lung Adenocarcinoma Cells Under a Time-Restricted Feeding-Mimicking Regimen

作者全名："Fang, Gaofeng; Chen, Qianyao; Li, Jianling; Lian, Xuemei; Shi, Dan"

作者地址："[Chen, Qianyao; Li, Jianling; Lian, Xuemei; Shi, Dan] Chongqing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Chongqing, Peoples R China; [Chen, Qianyao; Li, Jianling; Lian, Xuemei; Shi, Dan] Chongqing Med Univ, Ctr Lipid Res, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing 400016, Peoples R China; [Shi, Dan] Chongqing Med Univ, Res Ctr Environm & Populat Hlth, Sch Publ Hlth, Chongqing, Peoples R China"

通信作者："Lian, XM; Shi, D (通讯作者)，Chongqing Med Univ, Sch Publ Hlth, Dept Nutr & Food Hyg, Chongqing, Peoples R China.; Lian, XM; Shi, D (通讯作者)，Chongqing Med Univ, Ctr Lipid Res, Key Lab Mol Biol Infect Dis, Minist Educ, Chongqing 400016, Peoples R China.; Shi, D (通讯作者)，Chongqing Med Univ, Res Ctr Environm & Populat Hlth, Sch Publ Hlth, Chongqing, Peoples R China."

来源：JOURNAL OF NUTRITION

ESI学科分类：AGRICULTURAL SCIENCES

WOS号：WOS:001188577800001

JCR分区：Q2

影响因子：3.7

年份：2024

卷号：154

期号：2

开始页：354

结束页：368

文献类型：Article

关键词：circadian rhythm; 6-h TRF-mimicking; in vitro; diurnal transcriptomes; lung adenocarcinoma; cancer cell line

摘要："Background: The processes of tumor growth and circadian rhythm are intimately intertwined; thus, rewiring circadian metabolism by timerestricted feeding (TRF) may contribute to delaying carcinogenesis. However, research on the effect of a TRF cellular regimen on cancer is lacking. Objective: Investigate the circadian signatures of TRF in lung cancer in vitro. Methods: We first developed a cellular paradigm mimicking in vivo TRF and collected cells for transcriptome analysis. We further confirmed the effect on tumor cells upon 6-h TRF-mimicking (6-h TRFM) by real-time PCR, Lumicycle experiments, CCK-8, and flow cytometry assays. Results: We found that A549 lung adenocarcinoma cells treated with 6-h TRFM conditions displayed robust diurnal rhythms of transcriptomes, as well as modulation of the core clock genes relative to other different cellular regimens used in this study, including the fasting -mimicking conditions (ie, short-term starvation) and the serum -free regime. Notably, pathway analysis of oscillating genes exclusively in 6-h TRFM showed that some circadian genes were enriched in tumor -related pathways, such as the oxytocin signaling pathway, HIF-1 signaling pathway, and pentose and glucuronate interconversions. Moreover, in line with the circadian pathway enrichment results, 6h TRFM robustly inhibited cell proliferation and induced cell apoptosis and cell cycle arrest in lung adenocarcinoma A549 cells, lung adenocarcinoma H460 cells, esophageal carcinoma Eca-109 cells, and breast adenocarcinoma MCF-7 cells. Conclusions: Our findings provide the first in vitro mimicking medium for TRF intervention and indicate that 6-h TRFM is sufficient to reprogram the circadian signatures of lung adenocarcinoma cells and inhibit the progression of multiple tumors."

基金机构：National Natural Science Foundation of China [8210120502]; China Postdoctoral Science Foundation [2021M693755]; Postdoctoral Fund of Chongqing Province [(2020) 379]; Science and Technology Research Program of Chongqing Municipal Education Commission [KJQN202300467]; CQMU Program for Youth Innovation in Future Medicine [W0085]

基金资助正文："This research was funded by the National Natural Science Foundation of China (No. 8210120502) , China Postdoctoral Science Foundation (2021M693755) , Postdoctoral Fund of Chongqing Province ( (2020) 379) , the Science and Technology Research Program of Chongqing Municipal Education Commission (No. KJQN202300467) , and the CQMU Program for Youth Innovation in Future Medicine (No. W0085) ."