Truong Son Dinh An, Wongwattanakul Molin, Proungvitaya Tanakorn, Limpaiboon Temduang, Roytrakul Sittiruk, Chua-On Daraporn, Tummanatsakun Doungdean, Proungvitaya Siriporn
Centre of Research and Development of Medical Diagnostic Laboratories, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand.
Faculty of Medical Laboratory Science, Danang University of Medical Technology and Pharmacy, Danang 550000, Vietnam.
J Clin Med. 2022 Jul 1;11(13):3826. doi: 10.3390/jcm11133826.
Cholangiocarcinoma (CCA), a malignancy of the biliary epithelium, can arise at any point in the biliary system. We previously reported that CIAPIN1 is detectable in the sera and that its overexpression was associated with poor prognosis and metastasis of CCA patients. In this study, we investigated further its expression in CCA tissues, biological functions, and related signaling pathways in CCA cells. First, we examined CIAPIN1 expression in CCA tissues of 39 CCA patients using immunohistochemistry (IHC). Then, CIAPIN1-related proteins expressed in CCA cells were identified using RNA interference (siRNA) and liquid chromatography-mass spectrometry (LC-MS/MS). To predict the functions and signaling pathways of CIAPIN1 in CCA cells, the identified proteins were analyzed using bioinformatics tools. Then, to validate the biological functions of CIAPIN1 in the CCA cell line, transwell migration/invasion assays were used. CIAPIN1 was overexpressed in CCA tissues compared with adjacent noncancerous tissues. Its overexpression was correlated with lymph node metastasis. Bioinformatic analyses predicted that CIAPIN1 is connected to the TGF-β/SMADs signaling pathway via nitric oxide synthase 1 (NOS1) and is involved in the metastasis of CCA cells. In fact, cell migration and invasion activities of the KKU-100 CCA cell line were significantly suppressed by CIAPIN1 gene silencing. Our results unravel its novel function and potential signaling pathway in metastasis of CCA cells. CIAPIN1 can be a poor prognostic factor and can be a promising target molecule for CCA chemotherapy.
胆管癌（CCA）是一种胆管上皮恶性肿瘤，可发生于胆管系统的任何部位。我们之前报道过，血清中可检测到CIAPIN1，其过表达与CCA患者的不良预后和转移相关。在本研究中，我们进一步研究了其在CCA组织中的表达、生物学功能以及在CCA细胞中的相关信号通路。首先，我们使用免疫组织化学（IHC）检测了39例CCA患者的CCA组织中CIAPIN1的表达。然后，使用RNA干扰（siRNA）和液相色谱-质谱联用（LC-MS/MS）鉴定了在CCA细胞中表达的与CIAPIN1相关的蛋白质。为了预测CIAPIN1在CCA细胞中的功能和信号通路，使用生物信息学工具对鉴定出的蛋白质进行了分析。然后，为了验证CIAPIN1在CCA细胞系中的生物学功能，使用了Transwell迁移/侵袭实验。与相邻的非癌组织相比，CIAPIN1在CCA组织中过表达。其过表达与淋巴结转移相关。生物信息学分析预测，CIAPIN1通过一氧化氮合酶1（NOS1）与TGF-β/SMADs信号通路相连，并参与CCA细胞的转移。事实上，CIAPIN1基因沉默显著抑制了KKU-100 CCA细胞系的细胞迁移和侵袭活性。我们的结果揭示了其在CCA细胞转移中的新功能和潜在信号通路。CIAPIN1可能是一个不良预后因素，并且可能是CCA化疗的一个有前景的靶分子。
