油酸结合的 FABP7 通过调节核脂滴形成促进神经胶质瘤细胞增殖,The FEBS Journal

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油酸结合的 FABP7 通过调节核脂滴形成促进神经胶质瘤细胞增殖
The FEBS Journal ( IF 5.5 ) Pub Date : 2022-11-03 , DOI: 10.1111/febs.16672
Banlanjo Abdulaziz Umaru ₁ , Yoshiteru Kagawa ₁ , Yuki Ohsaki ₂ , Yijun Pan ₁ , Chuck T Chen ₃ , Daniel K Chen ₃ , Toshiaki Abe ₁ , Subrata Kumar Shil ₁ , Hirofumi Miyazaki ₁ , Shuhei Kobayashi ₁ , Motoko Maekawa ₁ , Yui Yamamoto ₄ , Tunyanat Wannakul ₁ , Shuhan Yang ₁ , Richard P Bazinet ₃ , Yuji Owada ₁

Affiliation

脂肪酸结合蛋白 7 (FABP7) 是参与调节细胞内 FA 代谢的脂肪酸 (FA) 分子伴侣之一，在胶质母细胞瘤中高表达，其表达与患者预后下降有关。以前，我们证明 FABP7 需要其结合伙伴才能发挥其功能，并且 FABP7 的 FA 结合位点的突变会影响肿瘤生物学。在这里，我们探讨了 FA 配体结合对 FABP7 功能在肿瘤增殖中的作用，并研究了 FABP7 和配体相互作用在肿瘤生物学中的机制。我们发现，在几种 FA 处理中，油酸 (OA) 促进了表达 FABP7 的细胞的细胞增殖。反过来，OA 增加了 FABP7 核定位，FABP7-OA 复合物在细胞核中的积累诱导了核脂滴 (nLD) 的形成，以及 nLD 与早幼粒细胞白血病 (PML) 核体的共定位增加。此外，OA 通过组蛋白乙酰化增加表达 FABP7 的细胞中增殖相关基因的 mRNA 水平。有趣的是，这些 OA 增强功能在 FABP7 敲除细胞和突变体 FABP7 过表达细胞中被废除。因此，我们的研究结果表明，FABP7-OA 细胞内相互作用可能调节 nLD 形成和表观遗传状态，从而增强增殖调节基因的转录，最终驱动肿瘤细胞增殖。这些 OA 增强功能在 FABP7 敲除细胞和突变体 FABP7 过表达细胞中被废除。因此，我们的研究结果表明，FABP7-OA 细胞内相互作用可能调节 nLD 形成和表观遗传状态，从而增强增殖调节基因的转录，最终驱动肿瘤细胞增殖。这些 OA 增强功能在 FABP7 敲除细胞和突变体 FABP7 过表达细胞中被废除。因此，我们的研究结果表明，FABP7-OA 细胞内相互作用可能调节 nLD 形成和表观遗传状态，从而增强增殖调节基因的转录，最终驱动肿瘤细胞增殖。

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Oleic acid-bound FABP7 drives glioma cell proliferation through regulation of nuclear lipid droplet formation

Fatty acid-binding protein 7 (FABP7), one of the fatty acid (FA) chaperones involved in the modulation of intracellular FA metabolism, is highly expressed in glioblastoma, and its expression is associated with decreased patients' prognosis. Previously, we demonstrated that FABP7 requires its binding partner to exert its function and that a mutation in the FA-binding site of FABP7 affects tumour biology. Here, we explored the role of FA ligand binding for FABP7 function in tumour proliferation and examined the mechanism of FABP7 and ligand interaction in tumour biology. We discovered that among several FA treatment, oleic acid (OA) boosted cell proliferation of FABP7-expressing cells. In turn, OA increased FABP7 nuclear localization, and the accumulation of FABP7–OA complex in the nucleus induced the formation of nuclear lipid droplet (nLD), as well as an increase in colocalization of nLD with promyelocytic leukaemia (PML) nuclear bodies. Furthermore, OA increased mRNA levels of proliferation-related genes in FABP7-expressing cells through histone acetylation. Interestingly, these OA-boosted functions were abrogated in FABP7-knockout cells and mutant FABP7-overexpressing cells. Thus, our findings suggest that FABP7–OA intracellular interaction may modulate nLD formation and the epigenetic status thereby enhancing transcription of proliferation-regulating genes, ultimately driving tumour cell proliferation.

更新日期：2022-11-03

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