Abstract
Cholangiocarcinoma (CCA) arising from the neoplastic transformation of cholangiocytes with increasing incidence in the worldwide. Unfortunately, a large amount of CCA patients lost their chance for surgery because it is hard to diagnose in the early stages. Long non-coding RNAs (lncRNAs) is closely associated with development and progression of various malignant tumors. Hox transcript antisense intergenic (HOTAIR), a negative prognostic factor for patients with gastric, liver and pancreatic carcinoma. Its transcription levels and functional roles in CCA is still unknown. Therefore, we aimed to explore the effect of HOTAIR in CCA including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results showed that HOTAIR was highly expressed both in CCA tissue samples and cell lines compared with corresponding normal bile duct tissues and Human intrahepatic biliary epithelial cells (HIBEC). Its overexpression was closely correlated with Tumor size, TNM stage and postoperative recurrence in CCA patients. Moreover, up-regulation of HOTAIR has correlation with prognosis in CCA patients. Knockdown of HOTAIR by siRNAs significantly decreased the migration and invasion but increased apoptosis of CCA cells in vitro. Overall, our study revealed that HOTAIR may play as a new potential therapeutic target and forecast poor prognosis for this fatal disease.
Highlights
Cholangiocarcinoma (CCA) is a common malignant tumor arising from the neoplastic transformation of cholangiocytes with increasing incidence all over the world[1,2]
The expression of Hox transcript antisense intergenic (HOTAIR) was up-regulated in CCA cell lines compared to Human intrahepatic biliary epithelial cells (HIBEC) cells (Fig. 1B)
Up-regulated HOTAIR is negatively correlated with prognosis. 70 patients were divided into high HOTAIR expression group or low expression group
Summary
Cholangiocarcinoma (CCA) is a common malignant tumor arising from the neoplastic transformation of cholangiocytes with increasing incidence all over the world[1,2]. For patients with CCA, surgical resection remains the best therapeutic approach. With the advance of gene technology, it has been found that long non-coding RNAs (lncRNAs) is closely associated with development and progression of malignant tumours[4,5]. Many studies found that dysregulated expression of lncRNAs play imperative roles in cancer suppressor gene or oncogenes. Indicated that HOTAIR plays imperative roles in the modulation of cancer progression. In order to understand the functional role of HOTAIR in CCA development and progression, in our study, we investigated the expression levels of HOTAIR in CCA tissues and analyzed its connection to clinical and pathological characteristics. We investigated the crucial roles of HOTAIR in CCA by analyzing proliferation, apoptosis, migration, invasion and epithelial-mesenchymal transition (EMT) after silencing of HOTAIR in vitro
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