Energy stress-induced linc01564 activates the serine synthesis pathway and facilitates hepatocellular carcinogenesis
Energy stress-induced linc01564 activates the serine synthesis pathway and facilitates hepatocellular carcinogenesis
复制标题
能量应激诱导的linc01564激活丝氨酸合成途径并促进肝细胞癌变
DOI：
10.1038/s41388-021-01749-x
复制
发表时间：
2021-03
期刊：
影响因子：
8
通讯作者：
Mei Yide
中科院分区：
文献类型：
--
作者：
Zhang Guang;Yang Yang;Hu Hao;Liu Kaiyue;Li Bingyan;Zhu Yu;Wang Zhongyu;Wu Qingfa;Mei Yide
癌细胞在代谢应激条件下进行代谢适应以维持其生存和生长，但其潜在的机制在很大程度上仍不清楚。目前也不知道lncRNAs是否有助于癌细胞的这种代谢适应。在这里，我们证明了linc01564是由转录因子ATF4诱导的对葡萄糖剥夺的反应。Linc01564通过激活丝氨酸合成途径促进肝癌细胞在缺糖状态下的存活。在机制上，linc01564作为miR-107/103a-3p的竞争内源RNA，减弱miR-107/103a-3p对丝氨酸合成途径的限速酶PHGDH的抑制作用，从而导致PHGDH表达增加。此外，linc01564能够通过PHGDH促进肝细胞癌的发生。综上所述，这些发现表明linc01564在调节癌细胞的代谢适应中起着重要作用，同时也暗示linc01564可能成为癌症的治疗靶点。
Cancer cells undergo metabolic adaption to sustain their survival and growth under metabolic stress conditions, yet the underlying mechanism remains largely unclear. It is also not known if lncRNAs contribute to this metabolic adaption of cancer cells. Here we show that linc01564 is induced in response to glucose deprivation by the transcription factor ATF4. Linc01564 functions to facilitate hepatocellular carcinoma cell survival under glucose deprivation by activating the serine synthesis pathway. Mechanistically, linc01564 acts as a competing endogenous RNA for miR-107/103a-3p and attenuates the inhibitory effect of miR-107/103a-3p on PHGDH, the rate-limiting enzyme of the serine synthesis pathway, thereafter leading to increased PHGDH expression. Furthermore, linc01564 is able to promote hepatocellular carcinogenesis via PHGDH. Together, these findings suggest that linc01564 is an important player in the regulation of metabolic adaption of cancer cells and also implicate linc01564 as a potential therapeutic target for cancer.
登录
查看更多内容
影响因子：
5.6
作者：
Finnerty JR;Wang WX;Hébert SS;Wilfred BR;Mao G;Nelson PT
通讯作者：
Nelson PT
影响因子：
4.5
作者：
Nilsson LM;Forshell TZ;Rimpi S;Kreutzer C;Pretsch W;Bornkamm GW;Nilsson JA
通讯作者：
Nilsson JA
癌症中的长非编码 RNA：信号传导电路。
影响因子：
19
作者：
Lin C;Yang L
通讯作者：
Yang L
影响因子：
12.3
作者：
Marchese FP;Raimondi I;Huarte M
通讯作者：
Huarte M
影响因子：
14.8
作者：
Pacold ME;Brimacombe KR;Chan SH;Rohde JM;Lewis CA;Swier LJ;Possemato R;Chen WW;Sullivan LB;Fiske BP;Cho S;Freinkman E;Birsoy K;Abu-Remaileh M;Shaul YD;Liu CM;Zhou M;Koh MJ;Chung H;Davidson SM;Luengo A;Wang AQ;Xu X;Yasgar A;Liu L;Rai G;Westover KD;Vander Heiden MG;Shen M;Gray NS;Boxer MB;Sabatini DM
通讯作者：
Sabatini DM