Cholangiocarcinoma (CCA) is one of the most aggressive and lethal malignancies. Long noncoding RNAs (lncRNAs) are being found to play crucial roles in CCA progression. This work aims to investigate the roles of long intergenic non-protein coding RNA 667 (LINC00667) in progression of CCA. RT-qPCR and western blot were applied to detect gene expression. Clinical correlation and survival were analyzed by statistical methods. Overexpression and RNA interference approaches were used to investigate the effects of LINC00667 on CCA cells. Tumor xenograft assay was performed to detect the function of LINC00667 in vivo. Transcriptional regulation and competing endogenous RNA (ceRNA) mechanism were predicted via bioinformatics analysis. ChIP, luciferase reporter, and Ago2 RIP assays further confirmed the predicted results. Our data indicated that LINC00667 was highly expressed in CCA tissues and cells, and transcription factor Yin Yang 1 (YY1) induced LINC00667 expression in CCA cells. Up-regulated LINC00667 was significantly associated with lymph node metastasis, advanced TNM stage, and poor prognosis. Knockdown of LINC00667 suppressed the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT) of CCA cells, while overexpression of LINC00667 acquired opposite effects. Moreover, knockdown of LINC00667 inhibited tumor growth in vivo. In addition, LINC00667 was demonstrated to function as a ceRNA for miR-200c-3p, and then LINC00667 up-regulated pyruvate dehydrogenase kinase 1 (PDK1) to promote CCA development by inhibiting miR-200c-3p. These findings identified a pivotal role of LINC00667 in tumorigenesis and development of CCA. Targeting the YY1/LINC00667/miR-200c-3p/PDK1 axis may provide a new therapeutic strategy for CCA treatment.

胆管癌 (CCA) 是最具侵袭性和致死性的恶性肿瘤之一。已发现长链非编码 RNA (lncRNA) 在 CCA 进展中发挥关键作用。这项工作旨在研究长基因间非蛋白编码 RNA 667 (LINC00667) 在 CCA 进展中的作用。应用 RT-qPCR 和蛋白质印迹检测基因表达。通过统计学方法分析临床相关性和生存率。过表达和 RNA 干扰方法用于研究 LINC00667 对 CCA 细胞的影响。进行肿瘤异种移植试验以检测体内 LINC00667 的功能。通过生物信息学分析预测转录调控和竞争性内源性 RNA (ceRNA) 机制。ChIP、荧光素酶报告基因和 Ago2 RIP 检测进一步证实了预测结果。我们的数据表明LINC00667在CCA组织和细胞中高表达，转录因子Yin Yang 1 (YY1)诱导了LINC00667在CCA细胞中的表达。上调的LINC00667与淋巴结转移、晚期TNM分期和预后不良显着相关。LINC00667 的敲低抑制了 CCA 细胞的增殖、迁移、侵袭和上皮间质转化 (EMT)，而 LINC00667 的过表达则获得了相反的效果。此外，LINC00667 的敲低抑制了体内肿瘤的生长。此外，LINC00667 被证明可作为 miR-200c-3p 的 ceRNA，然后 LINC00667 通过抑制 miR-200c-3p 上调丙酮酸脱氢酶激酶 1 (PDK1) 以促进 CCA 的发展。这些发现确定了 LINC00667 在 CCA 的肿瘤发生和发展中的关键作用。