Department of Science and Research, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China.
Department of Nuclear Medicine, The Seventh People's Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200137, P.R. China.
Mol Med Rep. 2021 Feb;23(2). doi: 10.3892/mmr.2020.11788. Epub 2020 Dec 23.
Recent studies have reported that aberrant PR domain zinc finger protein 14 (PRDM14) expression is associated with the therapeutic sensitivity of cancer cells to drugs. However, its role in lung adenocarcinoma (LUAD) remains unclear. The present study aimed to determine the functions of knockdown or overexpression of PRDM14 in the chemosensitivity and glycolysis of LUAD cells. PRDM14 expression was analyzed in lung cancer tissues from patients resistant and sensitive to cisplatin (DDP), as well as in LUAD cell lines A549 and DDP‑resistant A549 (A549/DDP) using reverse transcription quantitative‑PCR and western blotting. Additionally, apoptosis was analyzed by flow cytometry, and flow cytometry and biochemical analysis was used to analyze glycolysis, indicated by glucose uptake and lactate release. The results of the present study demonstrated that PRDM14 expression was upregulated in patients with DDP‑resistant LUAD and DDP‑resistant cell lines. Overexpression of PRDM14 suppressed the sensitivity of A549 cells to DDP and silencing of PRDM14 using shRNA targeting PRDM14 promoted the sensitivity of A549/DDP cells to DDP, compared with that in the respective control groups. In mice with xenograft tumors, knockdown of PRDM14 using shRNA targeting PRDM14 inhibited the A549/DDP cell‑derived tumor growth compared with scramble shRNA. The results of the glycolysis assays demonstrated that PRDM14 silencing inhibited glucose uptake, lactate release and glucose transporter 1 expression in A549/DDP cells compared with those in the control cells. PRDM14 overexpression relieved the inhibitory effects of 3‑bromopyruvate, a potent glycolytic inhibitor for glycolysis, on glucose uptake and lactate release in A549 cells compared with those in the control cells. Therefore, the results of the present study suggested that PRDM14 may inhibit the chemosensitivity and promote glycolysis in human LUAD cells.
最近的研究报告称，异常的 PR 结构域锌指蛋白 14（PRDM14）表达与癌细胞对药物的治疗敏感性有关。然而，其在肺腺癌（LUAD）中的作用尚不清楚。本研究旨在确定 PRDM14 敲低或过表达对 LUAD 细胞化疗敏感性和糖酵解的作用。采用逆转录定量聚合酶链反应和蛋白质印迹法分析对顺铂（DDP）耐药和敏感的肺癌组织以及 LUAD 细胞系 A549 和 DDP 耐药 A549（A549/DDP）中 PRDM14 的表达。通过流式细胞术分析细胞凋亡，通过流式细胞术和生化分析分析糖酵解，以葡萄糖摄取和乳酸释放为指标。本研究结果表明，DDP 耐药 LUAD 患者和 DDP 耐药细胞系中 PRDM14 表达上调。与相应对照组相比，过表达 PRDM14 抑制 A549 细胞对 DDP 的敏感性，而靶向 PRDM14 的 shRNA 沉默 PRDM14 则促进 A549/DDP 细胞对 DDP 的敏感性。在荷瘤小鼠中，与 scramble shRNA 相比，靶向 PRDM14 的 shRNA 敲低 PRDM14 抑制 A549/DDP 细胞衍生的肿瘤生长。糖酵解试验的结果表明，与对照细胞相比，PRDM14 沉默抑制 A549/DDP 细胞的葡萄糖摄取、乳酸释放和葡萄糖转运蛋白 1 表达。PRDM14 过表达减轻了 3-溴丙酮酸（一种有效的糖酵解抑制剂）对 A549 细胞葡萄糖摄取和乳酸释放的抑制作用，与对照细胞相比。因此，本研究结果表明，PRDM14 可能抑制人 LUAD 细胞的化疗敏感性并促进糖酵解。
