Xu Yi, Yao Yue, Zhong Xiangyu, Leng Kaiming, Qin Wei, Qu Lijun, Cui Yunfu, Jiang Xingming
Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, China; The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, 150086, China.
The Key Laboratory of Myocardial Ischemia, Harbin Medical University, Ministry of Education, Harbin, Heilongjiang Province, 150086, China.
Biochem Biophys Res Commun. 2018 Feb 5;496(2):455-461. doi: 10.1016/j.bbrc.2018.01.077. Epub 2018 Jan 12.
Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with increasing worldwide incidence and is characterized by unfavorable prognosis due to its early invasive characteristics and poor response to chemotherapy or radiotherapy. Accumulating evidence has indicated that aberrantly expressed circular RNAs (circRNAs) are involved in cancer development and progression. However, their clinical values and biological roles in CCA remain unclear. Hsa_circ_0001649, a novel cancer-related circRNA, has been previously reported to be downregulated in hepatocellular carcinoma and gastric cancer. In the present study, qRT-PCR was carried out to measure the expression of hsa_circ_0001649 in CCA tissue samples and cell lines, and the correlation between hsa_circ_0001649 expression and clinicopathologic features was analyzed. The biological functions of hsa_circ_0001649 in CCA cells were evaluated both in vitro and in vivo. As a result, hsa_circ_0001649 was aberrantly downregulated in CCA tissues and cells, and this downregulation was associated with tumor size and differentiation grade in CCA. In addition, hsa_circ_0001649 overexpression caused tumor suppressive effects via inhibiting cell proliferation, migration and invasion; inducing cell apoptosis in KMBC and Huh-28 cells. On the contrary, silencing of hsa_circ_0001649 caused the opposite phenotypes. Furthermore, tumor xenograft study confirmed the in vitro results. Collectively, our findings suggest that hsa_circ_0001649 might be a rational CCA-related therapeutic target.
胆管癌（CCA）是侵袭性最强的恶性肿瘤之一，在全球范围内发病率不断上升，因其早期侵袭性特征以及对化疗或放疗反应不佳，预后不良。越来越多的证据表明，异常表达的环状RNA（circRNA）参与癌症的发生和发展。然而，它们在CCA中的临床价值和生物学作用仍不清楚。Hsa_circ_0001649是一种新的癌症相关circRNA，此前有报道称其在肝细胞癌和胃癌中表达下调。在本研究中，采用qRT-PCR检测hsa_circ_0001649在CCA组织样本和细胞系中的表达，并分析hsa_circ_0001649表达与临床病理特征之间的相关性。在体外和体内评估了hsa_circ_0001649在CCA细胞中的生物学功能。结果显示，hsa_circ_0001649在CCA组织和细胞中异常下调，且这种下调与CCA的肿瘤大小和分化程度相关。此外，hsa_circ_0001649过表达通过抑制细胞增殖、迁移和侵袭，诱导KMBC和Huh-28细胞凋亡发挥肿瘤抑制作用。相反，沉默hsa_circ_0001649则导致相反的表型。此外，肿瘤异种移植研究证实了体外实验结果。总之，我们的研究结果表明，hsa_circ_0001649可能是一个合理的与CCA相关的治疗靶点。
