过去几十年来，肝细胞癌（HCC）的发病率和相关死亡有所增加。然而，HCC 发病机制的分子机制尚不完全清楚。长链非编码RNA（lncRNA）RP11-495P10.1已被证明与前列腺癌的进展密切相关，但其在HCC中的作用和具体机制仍不清楚。在这里，我们发现 RP11-495P10.1 在 HCC 组织和细胞中高表达，并有助于 HCC 细胞的增殖。此外，这项研究表明，RP11-495P10.1通过负向调节核受体亚家族4组a成员3（NR4A3）的表达来影响HCC的增殖。糖代谢重编程是肿瘤细胞的主要特征之一。在本研究中，我们发现RP11-495P10.1通过改变丙酮酸脱氢酶激酶1（PDK1）和丙酮酸脱氢酶（PDH）的表达来调节糖代谢重编程，从而促进HCC细胞的增殖。此外，敲低 RP11-495P10.1 通过促进 PDH 活性和乙酰辅酶 A 的产生来增加 NR4A3 启动子中 H3K27Ac 的富集，从而导致 NR4A3 转录增加。总之，RP11-495P10.1通过PDK1/PDH轴调节葡萄糖代谢的重编程和NR4A3启动子的乙酰化来促进HCC细胞增殖，这为HCC的诊断和治疗提供了一种以lncRNA为导向的治疗策略。

The incidence and related death of hepatocellular carcinoma (HCC) have increased over the past decades. However, the molecular mechanisms underlying HCC pathogenesis are not fully understood. Long noncoding RNA (lncRNA) RP11-495P10.1 has been proven to be closely associated with the progression of prostate cancer, but its role and specific mechanism in HCC are still unknown. Here, we identify that RP11-495P10.1 is highly expressed in HCC tissues and cells and contributes to the proliferation of HCC cells. Moreover, this study demonstrates that RP11-495P10.1 affects the proliferation of HCC by negatively regulating the expression of nuclear receptor subfamily 4 group a member 3 (NR4A3). Glycometabolism reprogramming is one of the main characteristics of tumor cells. In this study, we discover that RP11-495P10.1 regulates glycometabolism reprogramming by changing the expression of pyruvate dehydrogenase kinase 1 (PDK1) and pyruvate dehydrogenase (PDH), thus contributing to the proliferation of HCC cells. Furthermore, knockdown of RP11-495P10.1 increases enrichment of H3K27Ac in the promoter of NR4A3 by promoting the activity of PDH and the production of acetyl-CoA, which leads to the increased transcription of NR4A3. Altogether, RP11-495P10.1 promotes HCC cell proliferation by regulating the reprogramming of glucose metabolism and acetylation of the NR4A3 promoter via the PDK1/PDH axis, which provides an lncRNA-oriented therapeutic strategy for the diagnosis and treatment of HCC.