LncRP11-675F6.3 responds to rapamycin treatment and reduces triglyceride accumulation via interacting with HK1 in hepatocytes by regulating autophagy and VLDL-related proteins.
LncRP11-675F6.3 responds to rapamycin treatment and reduces triglyceride accumulation via interacting with HK1 in hepatocytes by regulating autophagy and VLDL-related proteins.
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DOI：
10.3724/abbs.2023091
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发表时间：
2023-10-25
影响因子：
3.7
通讯作者：
Liu L
中科院分区：
文献类型：
--
作者：
Wang L;Fang X;Yang Z;Li X;Cheng M;Cheng L;Wang G;Li W;Liu L
长链非编码RNA（lncRNA）已被广泛证实参与肝脏脂质稳态。在此，我们在HepG 2细胞中使用微阵列鉴定了响应于雷帕霉素处理的上调的lncRNA，命名为lncRP 11 -675F6.3。IncRP 11 - 675 F6的敲除。3导致载脂蛋白100（ApoB 100）、微粒体甘油三酯转移蛋白（MTTP）、ApoE和ApoC 3显著降低，细胞甘油三酯水平和自噬增加。此外，我们发现当lncRP 11 - 675 F6时，ApoB 100与GFP-LC 3在自噬体中明显共定位。3被敲低，表明可能与自噬相关的甘油三酯积累升高诱导ApoB 100降解并损害极低密度脂蛋白（VLDL）组装。然后，我们鉴定并验证了己糖激酶1（HK 1）作为lncRP 11 -675F6.3的结合蛋白，并介导甘油三酯调节和细胞自噬。更重要的是，我们发现lncRP 11 -675F6.3和HK 1通过调节VLDL相关蛋白和自噬来减轻高脂饮食诱导的非酒精性脂肪肝病（NAFLD）。总之，本研究揭示lncRP 11 -675F6.3可能与其相互作用蛋白HK 1协同参与mTOR信号通路的下游和肝脏甘油三酯代谢的调控网络，这可能为脂肪肝疾病的治疗提供新的靶点。
Long noncoding RNAs (lncRNAs) have been widely proven to be involved in liver lipid homeostasis. Herein, we identify an upregulated lncRNA named lncRP11-675F6.3 in response to rapamycin treatment using a microarray in HepG2 cells. Knockdown of lncRP11-675F6. 3 leads to a significant reduction in apolipoprotein 100 (ApoB100), microsomal triglyceride transfer protein (MTTP), ApoE and ApoC3 with increased cellular triglyceride level and autophagy. Furthermore, we find that ApoB100 is obviously colocalized with GFP-LC3 in autophagosomes when lncRP11-675F6. 3 is knocked down, indicating that elevated triglyceride accumulation likely related to autophagy induces the degradation of ApoB100 and impairs very low-density lipoprotein (VLDL) assembly. We then identify and validate that hexokinase 1 (HK1) acts as the binding protein of lncRP11-675F6.3 and mediates triglyceride regulation and cell autophagy. More importantly, we find that lncRP11-675F6.3 and HK1 attenuate high fat diet induced nonalcoholic fatty liver disease (NAFLD) by regulating VLDL-related proteins and autophagy. In conclusion, this study reveals that lncRP11-675F6.3 is potentially involved in the downstream of mTOR signaling pathway and the regulatory network of hepatic triglyceride metabolism in cooperation with its interacting protein HK1, which may provide a new target for fatty liver disorder treatment.
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影响因子：
20.1
作者：
Amengual J;Guo L;Strong A;Madrigal-Matute J;Wang H;Kaushik S;Brodsky JL;Rader DJ;Cuervo AM;Fisher EA
通讯作者：
Fisher EA
DOI：
10.1002/hep.29654
发表时间：
2018-05
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Liu C;Yang Z;Wu J;Zhang L;Lee S;Shin DJ;Tran M;Wang L
通讯作者：
Wang L
影响因子：
4.4
作者：
van Solingen C;Scacalossi KR;Moore KJ
通讯作者：
Moore KJ
影响因子：
3
作者：
Ehsani, Rezvan;Drablos, Finn
通讯作者：
Drablos, Finn
影响因子：
64.8
作者：
Hon CC;Ramilowski JA;Harshbarger J;Bertin N;Rackham OJ;Gough J;Denisenko E;Schmeier S;Poulsen TM;Severin J;Lizio M;Kawaji H;Kasukawa T;Itoh M;Burroughs AM;Noma S;Djebali S;Alam T;Medvedeva YA;Testa AC;Lipovich L;Yip CW;Abugessaisa I;Mendez M;Hasegawa A;Tang D;Lassmann T;Heutink P;Babina M;Wells CA;Kojima S;Nakamura Y;Suzuki H;Daub CO;de Hoon MJ;Arner E;Hayashizaki Y;Carninci P;Forrest AR
通讯作者：
Forrest AR