Gallbladder cancer (GBC) is the most malignant cancer of the biliary tract cancer and presents poor prognosis. CircRNAs have been identified as critical regulators of multiple stages in tumor progression. In the study, we first demonstrated that circular RNA circβ-catenin expression was upregulated in GBC tissues when compared to adjacent normal tissues and associated with advanced clinical stage and poor prognosis in GBC patients. Silencing of circβ-catenin obviously suppressed GBC cell proliferation and cell cycle progression in vitro, but circβ-catenin overexpression had the opposite effects. In vivo, silencing of circβ-catenin inhibited tumor growth. Furthermore, we also found that circβ-catenin promoted GBC cell lactate production, pyruvate production, ATP quantity, and extracellular acidification rate (ECAR), which suggested that circβ-catenin regulated Warburg effect in GBC. Mechanistic analysis further highlighted that circβ-catenin promoted Stathmin 1 (STMN1) expression through sponging miR-223 in GBC progression. In addition, knockdown of STMN1 inhibited cell growth and Warburg effect in GBC. In summary, our findings indicated that circβ-catenin/miR-223/STMN1 axis could regulate cell growth and Warburg effect in GBC. Targeting circβ-catenin might be a potential therapeutic strategy for GBC.

胆囊癌（GBC）是胆道癌中恶性程度最高的癌症，预后较差。circRNA 已被确定为肿瘤进展多个阶段的关键调节因子。在这项研究中，我们首先证明，与邻近的正常组织相比，GBC 组织中的环状 RNA circβ-catenin 表达上调，并且与 GBC 患者的晚期临床分期和不良预后相关。circβ-catenin 的沉默在体外明显抑制 GBC 细胞增殖和细胞周期进程，但 circβ-catenin 过表达具有相反的效果。在体内，circβ-catenin 的沉默抑制了肿瘤生长。此外，我们还发现 circβ-catenin 促进 GBC 细胞乳酸生成、丙酮酸生成、ATP 数量和细胞外酸化率 (ECAR)，这表明 circβ-catenin 调节了 GBC 中的 Warburg 效应。机制分析进一步强调，circβ-catenin 在 GBC 进展中通过海绵 miR-223 促进 Stathmin 1 (STMN1) 表达。此外，敲除 STMN1 可抑制 GBC 中的细胞生长和 Warburg 效应。总之，我们的研究结果表明，circβ-catenin/miR-223/STMN1 轴可以调节 GBC 中的细胞生长和 Warburg 效应。靶向 circβ-catenin 可能是 GBC 的潜在治疗策略。我们的研究结果表明，circβ-catenin/miR-223/STMN1 轴可以调节 GBC 中的细胞生长和 Warburg 效应。靶向 circβ-catenin 可能是 GBC 的潜在治疗策略。我们的研究结果表明，circβ-catenin/miR-223/STMN1 轴可以调节 GBC 中的细胞生长和 Warburg 效应。靶向 circβ-catenin 可能是 GBC 的潜在治疗策略。