多形性腺瘤基因1 （PLAG1）保护p53-/-肌上皮细胞免受缺氧引起的线粒体相关凋亡

IF 0.4 Q4 DENTISTRY, ORAL SURGERY & MEDICINE

Journal of Oral and Maxillofacial Surgery Medicine and Pathology Pub Date : 2025-01-23 DOI:10.1016/j.ajoms.2025.01.005

Nodoka Kindaichi, Yoshiki Mukudai, Yuzo Abe, Masataka Watanabe, Maki Nara, Konomi Yamada, Asami Houri, Toshikazu Shimane, Tatsuo Shirota

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引用次数: 0

摘要

目的多形性腺瘤（PA）是涎腺最常见的良性肿瘤之一。尽管多形性腺瘤基因1 （PLAG1）被认为与PA的癌变有关，但其在肌上皮细胞中的作用仍知之甚少。本研究探讨了缺氧时p53缺失时PLAG1在细胞凋亡通路中的内在参与。方法小鼠肌上皮细胞（ME）来源于p53-/-小鼠。细胞在无血清培养基中，在5 % CO2和100 %湿度的气氛中生长。低氧条件设置为37°C， 2 % O2和5 % CO2。采用3-（4,5-二甲基噻唑-2-基）-2,5-二苯基溴化四唑（MTT）和细胞周期法分别测定细胞活力和细胞增殖。采用caspase-3/7、线粒体膜电位（MMP）检测和western blot检测凋亡相关蛋白。在基因敲低实验中，用脂肪转染法将小干扰rna （siRNA）转染到细胞中。结果splag1在HIF-1α下游受到调控，在缺氧条件下通过Bcl-2通路抑制和/或抵抗细胞凋亡，这一过程经常在PAs中心被观察到。结论缺氧环境下肌上皮细胞PLAG1表达增加，bcl -2相关通路和MMP被激活。

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Pleomorphic adenoma gene 1 (PLAG1) protects p53-/- myoepithelial cells from mitochondria-related apoptosis caused by hypoxia

Objective

Pleomorphic adenoma (PA) is one of the most frequent benign tumors of the salivary glands. Although pleomorphic adenoma gene 1 (PLAG1) is considered to be responsible for the oncogenesis of a PA, its role in myoepithelial cells remains poorly understood. This study investigated the intrinsic involvement of PLAG1 in the apoptosis pathway at hypoxia in the absence of p53.

Methods

Mouse myoepithelial (ME) cells were derived from p53^-/- mice. The cells were grown in serum-free medium in an atmosphere of 5 % CO₂ and 100 % humidity. Hypoxic conditions were set at 37°C, 2 % O₂, and 5 % CO₂. Cell viability and cell proliferation were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and cell cycle assay, respectively. Apoptosis was assessed by caspase-3/7 and mitochondrial membrane potential (MMP) assays and western blotting for apoptosis-related proteins. In gene knockdown experiments, small interference RNAs (siRNA) were transfected into cells using the lipofection method.

Results

PLAG1 is regulated downstream of HIF-1α and shows potential to inhibit and/or resist apoptosis via the modulation of the Bcl-2 pathway under hypoxic conditions, which is often observed at the center of PAs.