Xie Kai, Feng Jian, Fan Dingwei, Wang Shi, Luo Jing, Ren Zhijian, Zheng Chao, Diao Yifei, De Mello Ramon Andrade, Tavolari Simona, Brandi Giovanni, Roden Anja C, Ren Binhui, Shen Yi, Xu Lin
Department of Cardiothoracic Surgery, Jinling Hospital, School of Nanjing Medical University, Nanjing, China.
Department of Thoracic Surgery, The Affiliated Cancer Hospital of Nanjing Medical University & Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research, Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Nanjing, China.
Transl Lung Cancer Res. 2022 Jul;11(7):1405-1419. doi: 10.21037/tlcr-22-465.
Metabolic reprogramming is an emerging cancer feature that has recently drawn special attention since it promotes tumor cell growth and proliferation. However, the mechanism of the Warburg effect is still largely unknown. This research aimed to reveal the effects of BarH-like homeobox 2 () in regulating tumor progression and glucose metabolism in lung adenocarcinoma (LUAD).
Expression of was measured by quantitative real-time polymerase chain reaction (qRT-PCR) in LUAD cell line and tissues, and the tumor-promoting function of in LUAD cells was detected and xenograft models. The metabolic effects of were examined by detecting glucose uptake, the production levels of lactate and pyruvate, and the extracellular acidification rate (ECAR). Chromatin immunoprecipitation (ChIP) assay and luciferase reporter gene assay were used to identify the underlying molecular mechanism of regulation of . Further studies showed that transcription factor directly interacts with and promotes the transcriptional activity of .
was remarkably up-regulated in LUAD tissues and positively linked to advanced clinical stage and poor prognosis. and data indicated ectopic expression of enhanced cell proliferation and tumorigenesis, whereas knockdown suppressed these effects. Metabolic-related experiments showed promoted the reprogramming of glucose metabolism. Mechanistically, the axis promoted LUAD progression and energy metabolism reprogramming.
In summary, our research first defined as a tumor-promoting factor in LUAD and that it may act as a novel prognostic biomarker and new therapeutic target for the disease.
代谢重编程是一种新出现的癌症特征，因其促进肿瘤细胞生长和增殖，最近受到了特别关注。然而，瓦伯格效应的机制仍 largely 未知。本研究旨在揭示类 BarH 同源盒 2（）在调节肺腺癌（LUAD）肿瘤进展和葡萄糖代谢中的作用。
通过定量实时聚合酶链反应（qRT-PCR）检测 LUAD 细胞系和组织中 的表达，并在 和 异种移植模型中检测 对 LUAD 细胞的促肿瘤功能。通过检测葡萄糖摄取、乳酸和丙酮酸的产生水平以及细胞外酸化率（ECAR）来研究 的代谢作用。采用染色质免疫沉淀（ChIP）分析和荧光素酶报告基因分析来确定 调控 的潜在分子机制。进一步研究表明，转录因子 直接与 相互作用并促进 的转录活性。
在 LUAD 组织中显著上调，且与晚期临床分期和不良预后呈正相关。 和 数据表明， 的异位表达增强了细胞增殖和肿瘤发生，而 敲低则抑制了这些作用。代谢相关实验表明 促进了葡萄糖代谢的重编程。从机制上讲， 轴促进了 LUAD 的进展和能量代谢重编程。
总之，我们的研究首次将 定义为 LUAD 中的促肿瘤因子，它可能作为该疾病的一种新型预后生物标志物和新的治疗靶点。
