LINC01714 Enhances Gemcitabine Sensitivity by Modulating FOXO3 Phosphorylation in Cholangiocarcinoma

Abstract

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.