Institute of Oral Biology, College of Dentistry, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
Department of Dentistry, College of Dentistry, National Yang Ming Chiao Tung University, Taipei 112, Taiwan.
Int J Mol Sci. 2021 Oct 29;22(21):11731. doi: 10.3390/ijms222111731.
Oral squamous cell carcinoma (OSCC) is among the leading causes of cancer-associated death worldwide. is an oncogenic miRNA in OSCC. NUMB is an adaptor protein capable of suppressing malignant transformation. Disruption of the - regulatory axis has been demonstrated in malignancies. Mitochondrial dysfunction and adaptation to glycolytic respiration are frequent events in malignancies. Monocarboxylate transporters (MCTs) function to facilitate lactate flux in highly glycolytic cells. Upregulation of and has been shown to be a prognostic factor of OSCC. Here, we reported that can modulate glycolysis in OSCC. Using the CRISPR/Cas9 gene editing strategy, we identified increases in oncogenic phenotypes, and expression, lactate production, and glycolytic respiration in -deleted OSCC subclones. Transfection of the or isoform reversed the oncogenic induction elicited by deletion. This study also showed, for the first time, that NUMB4 binds MCT1 and MCT4 and that this binding increases their ubiquitination, which may decrease their abundance in cell lysates. The disruptions in oncogenicity and metabolism associated with deletion and deletion were partially rescued by / expression or knockdown. This study demonstrated that NUMB is a novel binding partner of MCT1 and MCT4 and that the -- regulatory cascade is present in oral carcinoma.
口腔鳞状细胞癌 (OSCC) 是全球癌症相关死亡的主要原因之一。 是 OSCC 中的一种致癌 miRNA。NUMB 是一种能够抑制恶性转化的衔接蛋白。已经在恶性肿瘤中证明了 - 调节轴的破坏。线粒体功能障碍和对糖酵解呼吸的适应是恶性肿瘤中的常见事件。单羧酸转运蛋白 (MCT) 的功能是促进高度糖酵解细胞中的乳酸通量。上调 和 已被证明是 OSCC 的预后因素。在这里，我们报告 可以调节 OSCC 中的糖酵解。使用 CRISPR/Cas9 基因编辑策略，我们鉴定出 - 缺失的 OSCC 亚克隆中致癌表型、 和 表达、乳酸产生和糖酵解呼吸增加。转染 或 同工型逆转了 缺失引起的致癌诱导。这项研究还首次表明 NUMB4 结合 MCT1 和 MCT4，并且这种结合增加了它们的泛素化，这可能会降低它们在细胞裂解物中的丰度。通过 / 表达或敲低，与 缺失和 缺失相关的致癌性和代谢紊乱部分得到挽救。这项研究表明 NUMB 是 MCT1 和 MCT4 的新型结合伴侣，并且 -- 调节级联存在于口腔癌中。
