Caveolin-1 (CAV1), a major structural protein of caveolae, is reported to exert a positive regulatory effect on tumor growth and to play a crucial role in hepatocellular carcinoma (HCC) cell metastasis by regulating glycosyltransferase expression and cellular glycosylation. However, the role of CAV1 in modulating protein glycosylation and tumor metastasis remains to be further elucidated. In the present study, we showed that CAV1 promoted the expression of O-GlcNAc transferase (OGT), which catalyzed the addition of O-GlcNAc residues to a variety of nuclear and cytoplasmic proteins. In human HCC cell lines with different metastatic potentials, high levels of OGT and cellular O-GlcNAcylation were associated with CAV1 expression and cell metastasis. Overexpression of CAV1 increased the levels of OGT and O-GlcNAcylation, and cell migration was also increased. Furthermore, CAV1 was found to reduce the expression of Runt‑related transcription factor 2 (RUNX2) in HCC cells. Subsequently, this effect resulted in the attenuation of the RUNX2-induced transcription of microRNA24 (miR24), a microRNA previously shown to suppress OGT mRNA expression by targeting its 3′ untranslated regions (UTR). Finally, we demonstrated that CAV1 induced cellular O-GlcNAcylation and HCC cell invasion. This study provides evidence of CAV1-mediated increases in OGT expression and O-GlcNAcylation. These data provide insight into a novel mechanism underlying HCC metastasis and suggest a novel strategy for the treatment of HCC.

中文翻译：

---

Caveolin-1上调OGT促进肝癌细胞迁移和侵袭

据报道，Caveolin-1 (CAV1) 是小窝的主要结构蛋白，通过调节糖基转移酶表达和细胞糖基化，对肿瘤生长发挥积极调节作用，并在肝细胞癌 (HCC) 细胞转移中发挥关键作用。然而，CAV1在调节蛋白质糖基化和肿瘤转移中的作用仍有待进一步阐明。在本研究中，我们发现 CAV1 促进了O -GlcNAc 转移酶 (OGT) 的表达，该酶催化O -GlcNAc 残基添加到各种核和细胞质蛋白中。在具有不同转移潜能的人 HCC 细胞系中，高水平的 OGT 和细胞O-GlcNAcylation 与 CAV1 表达和细胞转移有关。CAV1的过表达增加了OGT和O -GlcNAcylation的水平，并且细胞迁移也增加了。此外，发现 CAV1 可降低 HCC 细胞中 Runt 相关转录因子 2 (RUNX2) 的表达。随后，这种效应导致 RUNX2 诱导的 microRNA24 (miR24) 转录减弱，miR24 是一种先前显示通过靶向其 3' 非翻译区 (UTR)来抑制OGT mRNA 表达的 microRNA。最后，我们证明了 CAV1 诱导细胞O -GlcNAcylation 和 HCC 细胞侵袭。该研究提供了 CAV1 介导的 OGT 表达和 OGT 增加的证据。-GlcNA酰化。这些数据提供了对潜在 HCC 转移的新机制的洞察，并提出了一种治疗 HCC 的新策略。