Department of Cancer Intervention, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
Department of Pathology, Seventh People's Hospital of Shanghai University of TCM, Shanghai, China.
Cell Cycle. 2022 Oct;21(19):2079-2090. doi: 10.1080/15384101.2022.2085359. Epub 2022 Jun 7.
Cholangiocarcinoma (CCA) is one of the most common hepatic and biliary malignancies. The overall five-year survival rate for cholangiocarcinoma is less than 15%. miR-28-5p has been reported to participate the development of various human cancer types. But whether miR-28-5p is associated with the clinical course of CCA patients has not been clarified. Herein, we observed that miR-28-5p was reduced in CCA tissues and predicts the poor prognosis of CCA patients. Treatment with the demethylating agent 5-aza-2'-deoxycytidine (5-AZA) restored miR-28-5p expression in CCA cell lines. Furthermore, up-regulated miR-28-5p inhibited CCA cells growth and metastasis. Mechanistically, miR-28-5p suppressed CCA cells growth and metastasis via directly targeting CD44 molecular. Specific CD44 special siRNA abrogated the discrepancy of the proliferation and metastasis capacity between miR-28-5p-overexpression CCA cells and their control cells, which further confirmed that CD44 was required in miR-28-5p-inhibited CCA cell growth and metastasis.
胆管癌（CCA）是最常见的肝和胆道恶性肿瘤之一。胆管癌的总体五年生存率低于 15%。miR-28-5p 已被报道参与多种人类癌症类型的发展。但是，miR-28-5p 是否与 CCA 患者的临床病程有关尚未阐明。在此，我们观察到 miR-28-5p 在 CCA 组织中减少，并预测 CCA 患者的预后不良。用去甲基化剂 5-氮杂-2'-脱氧胞苷（5-AZA）处理可恢复 CCA 细胞系中的 miR-28-5p 表达。此外，上调的 miR-28-5p 抑制 CCA 细胞的生长和转移。在机制上，miR-28-5p 通过直接靶向 CD44 分子抑制 CCA 细胞的生长和转移。特异性 CD44 特殊 siRNA 消除了 miR-28-5p 过表达 CCA 细胞与其对照细胞之间增殖和转移能力的差异，这进一步证实 CD44 是 miR-28-5p 抑制 CCA 细胞生长和转移所必需的。
