Long noncoding RNAs (lncRNAs) have been shown to play crucial roles in human cancers. However, the underlying biological functions and mechanisms of lncRNAs in cholangiocarcinoma (CCA) remain largely unknown. We aimed to characterize the transcriptional landscape of lncRNAs in CCA and identify lncRNAs that were able to serve as prognosis markers and therapeutic targets for CCA. Here, we investigated the transcriptional landscape and dysregulation of lncRNAs in CCA. LINC01714 was found to be recurrently downregulated in CCA tumor samples. Our results revealed that decreased LINC01714 expression was associated with the poor survival of CCA patients. Our observations revealed that LINC01714 suppressed the proliferation, migration, and invasion abilities of CCA cells both in vitro and in vivo. Furthermore, we found that LINC01714 physically interacted with Forkhead Box O3 (FOXO3) and increased the FOXO3 protein level. In addition, LINC01714 could decrease the phosphorylation level of FOXO3. Interestingly, LINC01714 was able to enhance the sensitivity to gemcitabine in CCA tumor cells through modulating phosphorylated FOXO3-Ser318. Our study revealed LINC01714 as a promising prognostic indictor for patients with CCA, provided insights into the molecular pathogenesis of CCA, and also showed that LINC01714 is a potential therapeutic combination for gemcitabine in CCA treatment.

长的非编码RNA（lncRNA）已显示在人类癌症中起关键作用。然而，在胆管癌（CCA）中lncRNA的潜在生物学功能和机制仍是未知之数。我们旨在表征CCA中lncRNA的转录情况，并鉴定能够用作CCA的预后标志物和治疗靶标的lncRNA。在这里，我们调查了CCA中lncRNA的转录态势和失调。发现CCA肿瘤样品中LINC01714反复下调。我们的结果表明，LINC01714表达降低与CCA患者生存率低有关。我们的观察结果表明，LINC01714在体外和体内均抑制了CCA细胞的增殖，迁移和侵袭能力。。此外，我们发现LINC01714与Forkhead Box O3（FOXO3）发生了物理相互作用，并增加了FOXO3蛋白水平。此外，LINC01714可以降低FOXO3的磷酸化水平。有趣的是，LINC01714能够通过调节磷酸化的FOXO3-Ser318来增强CCA肿瘤细胞对吉西他滨的敏感性。我们的研究显示LINC01714是CCA患者有希望的预后指标，为CCA的分子发病机理提供了见识，并且还表明LINC01714是吉西他滨在CCA治疗中的潜在治疗组合。