Background

Circular RNA (circRNA) has been demonstrated to play key roles in regulating glioma progression. Understanding the regulatory mechanism of circRNA in glioma is vital to reveal the pathogenesis of glioma and develop novel therapeutic strategies. Therefore, our study focuses on the role and underlying mechanism of Circ_CLIP2 in glioma.

Methods

The expression of Circ_CLIP2, miR-195-5p and HMGB3 in glioma cells and tissues were analyzed using qRT-PCR. Cell proliferation was determined with colony formation and MTT assays. Cell cycle and apoptosis were examined by flow cytometry. Western blot was conducted for analyzing HMGB3, PCNA, Bax, Bcl-2, cleaved-caspase 3, Wnt-1 and β-catenin. Dual-luciferase reporter assay was measured to investigate the interaction among Circ_CLIP2, miR-195-5p and HMGB3.

Results

The expression of Circ_CLIP2 and HMGB3 were increased while miR-195-5p was down-regulated in glioma cells and patients. Silencing of Circ_CLIP2 inhibited cell proliferation, enhanced cell apoptosis and inhibited the Wnt/β-catenin signaling pathway. Circ_CLIP2 suppressed miR-195-5p expression by directly sponging miR-195-5p. MiR-195-5p inhibited HMGB3 expression via directly targeting HMGB3. Knockdown of miR-195-5p facilitated cell proliferation, inhibited cell apoptosis and activated Wnt/β-catenin signaling, which were reversed by silencing of HMGB3.

Conclusion

Knockdown of Circ_CLIP2 suppresses glioma progression by targeting miR-195-5p/HMGB3 thus inhibiting Wnt/β-catenin signaling. This study may provide potential therapeutic targets against glioma.

中文翻译：

---

Circ_CLIP2 通过靶向 miR-195-5p/HMGB3 轴促进胶质瘤进展

背景

环状 RNA (circRNA) 已被证明在调节胶质瘤进展中起关键作用。了解 circRNA 在胶质瘤中的调控机制对于揭示胶质瘤的发病机制和开发新的治疗策略至关重要。因此，我们的研究重点是Circ_CLIP2在胶质瘤中的作用和潜在机制。

方法

使用 qRT-PCR 分析 Circ_CLIP2、miR-195-5p 和 HMGB3 在胶质瘤细胞和组织中的表达。用集落形成和MTT测定确定细胞增殖。通过流式细胞术检查细胞周期和细胞凋亡。进行蛋白质印迹以分析 HMGB3、PCNA、Bax、Bcl-2、cleaved-caspase 3、Wnt-1 和 β-catenin。测量双荧光素酶报告基因测定以研究 Circ_CLIP2、miR-195-5p 和 HMGB3 之间的相互作用。

结果

在胶质瘤细胞和患者中，Circ_CLIP2 和 HMGB3 的表达增加，而 miR-195-5p 的表达下调。Circ_CLIP2 的沉默抑制细胞增殖，增强细胞凋亡并抑制 Wnt/β-catenin 信号通路。Circ_CLIP2 通过直接海绵化 miR-195-5p 来抑制 miR-195-5p 的表达。MiR-195-5p 通过直接靶向 HMGB3 抑制 HMGB3 表达。敲低 miR-195-5p 可促进细胞增殖、抑制细胞凋亡并激活 Wnt/β-catenin 信号传导，这些可通过 HMGB3 的沉默来逆转。

结论

敲低 Circ_CLIP2 通过靶向 miR-195-5p/HMGB3 从而抑制 Wnt/β-catenin 信号传导来抑制胶质瘤进展。该研究可能提供针对胶质瘤的潜在治疗靶点。