Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma.
Fasting regulates mitochondrial function through lncRNA PRKCQ-AS1-mediated IGF2BPs in papillary thyroid carcinoma.
复制标题
在甲状腺乳头状癌中，禁食通过lncRNA PRKCQ-AS 1介导的IGF 2BPs调节线粒体功能。
DOI：
10.1038/s41419-023-06348-0
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发表时间：
2023-12-14
影响因子：
9
通讯作者：
Lv, Zhongwei
中科院分区：
文献类型：
--
作者：
Zhang, Xiaoping;Zhong, Yong;Liu, Lin;Jia, Chengyou;Cai, Haidong;Yang, Jianshe;Wu, Bo;Lv, Zhongwei
反复出现的证据表明，禁食在各种癌症中具有广泛的抗肿瘤作用，包括乳头状甲状腺癌（PTC）。然而，这种关系与PTC的潜在机制是未知的。在这项研究中，我们研究禁食对PTC糖酵解和线粒体功能的影响。我们发现，在抑制TPC细胞糖酵解和线粒体功能的过程中，禁食在体外和体内损害糖酵解并减少线粒体功能障碍，并且体外禁食和体内禁食模拟饮食（FMD）显著增加lncRNA-蛋白激酶C θ反义RNA 1（PRKCQ-AS 1）的表达。此外，lncRNA PRKCQ-AS 1在PTC组织和细胞中显著降低。此外，PRKCQ-AS 1过表达增加PTC细胞糖酵解和线粒体功能; PRKCQ-AS 1敲低具有相反的效果。在进一步的机制分析中，我们确定PRKCQ-AS 1与IGF 2BP物理相互作用并增强蛋白质精氨酸甲基转移酶7（PRMT 7）mRNA，这是PTC中调节糖酵解和线粒体功能的关键因素。因此，PRKCQ-AS 1抑制肿瘤生长，同时通过IGF 2BP/PRMT 7信号传导调节糖酵解和线粒体功能。这些结果表明，lncRNA PRKCQ-AS 1是禁食的关键下游靶标，并参与PTC代谢重编程。此外，PRKCQ-AS 1/IGF 2BPs/PRMT 7轴是PTC诊断和治疗的理想治疗靶点。
Recurring evidence suggests that fasting has extensive antitumor effects in various cancers, including papillary thyroid carcinoma (PTC). However, the underlying mechanism of this relationship with PTC is unknown. In this study, we study the effect of fasting on glycolysis and mitochondrial function in PTC. We find that fasting impairs glycolysis and reduces mitochondrial dysfunction in vitro and in vivo and also fasting in vitro and fasting mimicking diets (FMD) in vivo significantly increase the expression of lncRNA-protein kinase C theta antisense RNA 1 (PRKCQ-AS1), during the inhibition of TPC cell glycolysis and mitochondrial function. Moreover, lncRNA PRKCQ-AS1 was significantly lower in PTC tissues and cells. In addition, PRKCQ-AS1 overexpression increased PTC cell glycolysis and mitochondrial function; PRKCQ-AS1 knockdown has the opposite effect. On further mechanistic analysis, we identified that PRKCQ-AS1 physically interacts with IGF2BPs and enhances protein arginine methyltransferases 7 (PRMT7) mRNA, which is the key player in regulating glycolysis and mitochondrial function in PTC. Hence, PRKCQ-AS1 inhibits tumor growth while regulating glycolysis and mitochondrial functions via IGF2BPs/PRMT7 signaling. These results indicate that lncRNA PRKCQ-AS1 is a key downstream target of fasting and is involved in PTC metabolic reprogramming. Further, the PRKCQ-AS1/IGF2BPs/PRMT7 axis is an ideal therapeutic target for PTC diagnosis and treatment.
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DOI：
10.1126/science.1173635
发表时间：
2009-07-10
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Colman RJ;Anderson RM;Johnson SC;Kastman EK;Kosmatka KJ;Beasley TM;Allison DB;Cruzen C;Simmons HA;Kemnitz JW;Weindruch R
通讯作者：
Weindruch R
DOI：
10.1186/s41199-016-0021-x
发表时间：
2017-01-01
期刊：
Cancers of the head & neck
影响因子：
--
作者：
Hahn, Lewis D;Kunder, Christian A;Desser, Terry S
通讯作者：
Desser, Terry S
影响因子：
5.3
作者：
Hansen, TVO;Hammer, NA;Nielsen, FC
通讯作者：
Nielsen, FC
影响因子：
29
作者：
Brandhorst S;Choi IY;Wei M;Cheng CW;Sedrakyan S;Navarrete G;Dubeau L;Yap LP;Park R;Vinciguerra M;Di Biase S;Mirzaei H;Mirisola MG;Childress P;Ji L;Groshen S;Penna F;Odetti P;Perin L;Conti PS;Ikeno Y;Kennedy BK;Cohen P;Morgan TE;Dorff TB;Longo VD
通讯作者：
Longo VD
影响因子：
3.9
作者：
Harries, Lorna W.
通讯作者：
Harries, Lorna W.