Medical School, Kunming University of Science and Technology, Kumming, Yunnan, China; Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kumming, Yunnan, China.
Department of Hepatobiliary and Pancreatic Surgery, The First People's Hospital of Yunnan Province, Affiliated Hospital of Kunming University of Science and Technology, Kumming, Yunnan, China.
Tissue Cell. 2022 Jun;76:101756. doi: 10.1016/j.tice.2022.101756. Epub 2022 Feb 10.
Cholangiocarcinoma (CCA) is a primary biliary epithelium malignancy with limited therapies, poor prognosis and high mortality rate. Nowadays, the molecular mechanisms of CCA remain elusive. SPARC has been proposed to be highly expressed in clinical CCA tissues, but few studies has been elucidated its functions in CCA. In the current study, we aimed to investigate the functional role of SPARC in the progression of CCA. In this study, a significantly increased expression of SPARC was observed in CCA tissues and cells. Knockdown of SPARC by RNA interference significantly impeded the proliferation of CCA cells. Moreover, SPARC silencing hampered the migration and invasion of CCA cells by inhibiting EMT. In parallel, overexpression of SPARC in RBE cells had the opposite effects. Mechanically, SPARC promoted proliferation, migration, invasion, and EMT of CCA cells in vitro via activating the PI3K-AKT signaling. Overall, our integrated analysis revealed that SPARC plays a crucial role in CCA progression via the PI3K-AKT signaling pathway, which suggests that targeting SPARC might represent a promising approach for improving CCA patient's clinical outcome.
胆管癌（CCA）是一种原发性胆道上皮恶性肿瘤，治疗方法有限，预后差，死亡率高。目前，CCA 的分子机制仍不清楚。已有研究提出，富含半胱氨酸的酸性分泌蛋白（SPARC）在临床 CCA 组织中高表达，但对其在 CCA 中的功能研究甚少。本研究旨在探讨 SPARC 在 CCA 进展中的功能作用。本研究观察到 SPARC 在 CCA 组织和细胞中表达明显增加。RNA 干扰敲低 SPARC 显著抑制 CCA 细胞的增殖。此外，通过抑制 EMT，SPARC 沉默抑制了 CCA 细胞的迁移和侵袭。同时，在 RBE 细胞中过表达 SPARC 则产生了相反的效果。机制上，SPARC 通过激活 PI3K-AKT 信号通路促进 CCA 细胞的体外增殖、迁移、侵袭和 EMT。综上所述，我们的综合分析表明，SPARC 通过 PI3K-AKT 信号通路在 CCA 进展中发挥关键作用，提示靶向 SPARC 可能是改善 CCA 患者临床预后的一种有前途的方法。
