Overexpression of long noncoding RNA H19 indicates a poor prognosis for cholangiocarcinoma and promotes cell migration and invasion by affecting epithelial-mesenchymal transition.

Cholangiocarcinoma (CCA) is a deadly disease that poorly responds to chemotherapy and radiotherapy and whose incidence has increased worldwide. Furthermore, long noncoding RNAs (lncRNAs) play important roles in multiple biological processes, including tumorigenesis. Specifically, H19, the first discovered lncRNA, has been reported to be overexpressed in diverse human carcinomas, but the overall biological role and clinical significance of H19 in CCA remains unknown. In the present study, expression levels of H19 were investigated in CCA tissues and cell lines and were correlated with clinicopathological features. Moreover, we explored the functional roles of H19 depletion in QBC939 and RBE cells, including cell proliferation, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). The results indicated that H19 was upregulated in CCA tissue samples and cell lines, and this upregulation was associated with tumor size, TNM stage, postoperative recurrence and overall survival in 56 patients with CCA. Moreover, knockdown of H19 followed by RNA silencing restrained cell proliferation and promoted apoptosis. In addition, H19 suppression impaired migration and invasion potential by reversing EMT. Overall, our findings may help to develop diagnostic biomarkers and therapeutics that target H19 for the treatment of CCA.

Xu Y ，Wang Z ，Jiang X ，Cui Y ... -  《-》

Long non-coding RNA CCAT2 promotes cholangiocarcinoma cells migration and invasion by induction of epithelial-to-mesenchymal transition.

Cholangiocarcinoma (CCA) is one of the most aggressive malignancies in humans. Emerging evidence has indicated that abnormally expressed long non-coding RNAs (lncRNAs) could conduce to tumorigenesis and progression. Specifically, colon cancer-associated transcript 2 (CCAT2) has been reported to be overexpressed in several carcinomas. However, its clinical significance and functional roles in CCA is still unknown. qRT-PCR experiments were conducted to assess the CCAT2 expression in CCA tissue samples and cell lines. In addition, the link between CCAT2 expression and clinicopathological characteristics was analyzed. The potential effects of CCAT2 in CCA cells was evaluated in vitro including cell proliferation, colony-forming ability, apoptosis, migration, invasion and epithelial-to-mesenchymal transition (EMT). As a result, CCAT2 was aberrantly overexpressed in CCA tissue samples and cells, and this upregulation was correlated with tumor size, lymph node invasion, TNM stage and postoperative recurrence in CCA patients. Overexpression of CCAT2 could serve as an independent prognostic indicator for CCA. Additionally, overexpression of CCAT2 was a dismal prognostic indicator for patients with CCA. Furthermore, CCAT2 silencing caused tumor suppressive effects via reducing cell proliferation, migration and invasion, inducing cell apoptosis and reversing the EMT process in HuCCT1 and CCLP1 cells. Collectively, our data illustrated that lncRNA CCAT2 played an oncogenic role in CCA and may offer a potential therapeutic target for treating this fatal disease.

Xu Y ，Yao Y ，Qin W ，Zhong X ，Jiang X ，Cui Y ... -  《-》

Long non-coding RNA HOTAIR promotes tumorigenesis and forecasts a poor prognosis in cholangiocarcinoma.

Qin W ，Kang P ，Xu Y ，Leng K ，Li Z ，Huang L ，Gao J ，Cui Y ，Zhong X ... -  《Scientific Reports》

Up-regulated LINC00261 predicts a poor prognosis and promotes a metastasis by EMT process in cholangiocarcinoma.

LINC00261 plays a vital role in tumorigenesis and metastasis of digestive system cancer. However, an influence of LINC00261 on cholangiocarcinoma has a little research. There, we investigated clinical role and molecular mechanisms of LINC00261 in cholangiocarcinoma. The qRT-PCR was performed for the detection of LINC00261 level in 50 paired specimens from CCA patients and six cell lines. Cell proliferation were explored by CCK-8 and colony formation assays in QBC939 and RBE cells after transfected with si-LINC00261 or si-NC. Then, AO/EB double fluorescence staining and flow cytometric assays were performed to assess cell apoptosis. Transwell and wound healing assays were selected to evaluate migratory and invasive property of cells. Protein levels, such as PCNA, Bax, Bcl-2, and several epithelial-to-mesenchymal transition markers, including E-cadherin, N-cadherin and Vimentin, were detected by western blot assays. Furthermore, we use a R2 platform to evaluate the correlation between LINC00261 and EMT makers and predict the overall survival and relapse-free survival for CCA patients by the expression of LINC00261/ EMT makers. LINC00261 was overexpressed in cancerous tissues and CCA cell lines compared with adjacent tissues and HIBEC, respectively. Up-regulation of LINC00261 was related to larger tumor size (p = 0.009), positive lymph node metastasis (p = 0.021), advanced TNM stages (p = 0.017) and higher postoperative recurrence (p = 0.009) for CCA patients. Additionally, univariate and multivariate analysis displayed that LINC00261 an independent prognostic factor in CCA patients. Knockdown of LINC00261 expression in RBE and QBC939 cell lines inhibited cell proliferation, migration and invasion property and increased cell apoptosis and the EMT progression. Moreover, there was a strong correlation between LINC00261 and E-cadherin (CDH1) (p < 0.05), and low expression of E-cadherin (CDH1) has a poor overall survival and relapse-free survival in CCA patients (p < 0.05). Overall, high level of LINC00261 in CCA predicts a poor prognosis, and promotes a metastasis via EMT process. Thus, LINC00261 could be a promising biomarker and therapeutic target for CCA, and in the high level of LINC00261 in CCA, E-cadherin or CDH1 might be an effective factor for tumor metastasis or poor prognosis.

Gao J ，Qin W ，Kang P ，Xu Y ，Leng K ，Li Z ，Huang L ，Cui Y ，Zhong X ... -  《-》

Enhanced expression of lncRNA TP73-AS1 predicts adverse phenotypes for cholangiocarcinoma and exerts oncogenic properties in vitro and in vivo.

Cholangiocarcinoma (CCA) is one of the most aggressive malignancies with increasing incidence worldwide. Various evidence documents that abnormally expressed long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and progression. TP73-AS1 is a novel cancer-related lncRNA that contributes to the development of several malignancies. However, its clinical value and potential effects on CCA remains unknown. RT-qPCR was used to measure the expression levels of TP73-AS1 in CCA tissues and paired non-tumor tissues and the association between TP73-AS1 expression and clinicopathological characteristics was analyzed. In addition, the functional roles of TP73-AS1 in CCA were detected both in vitro and in vivo. The results illustrated that TP73-AS1 transcription is enhanced in both CCA tissue samples and cell lines, and this upregulation is closely associated with larger tumor size (p=0.008) and advanced TNM stage (p=0.026) in patients with CCA. For the part of functional assays, silencing of TP73-AS1 could attenuate CCA cell growth both in vitro and in vivo. Additionally, silencing of TP73-AS1 facilitates apoptosis via activating caspase-3 and caspase-9. Importantly, TP73-AS1 expression did not affect HIBEC cell growth and apoptosis. Moreover, TP73-AS1 could also facilitate migration and invasion potential of CCA cells. Collectively, these findings may help to develop a potential therapeutic target for the patients with CCA.

Yao Y ，Sun Y ，Jiang Y ，Qu L ，Xu Y ... -  《-》