Long non‐coding RNA ZEB1‐AS1 predicts

Emerging evidence suggests that long non‐coding RNAs (lncRNAs) play pivotal roles in cancer progression, including in intrahepatic cholangiocarcinoma (IHCC). The overexpression of lncRNA ZEB1 antisense 1 (ZEB1‐AS1) has been discovered in several types of cancer; however, the clinical significance and functional role of ZEB1‐AS1 in IHCC have not yet been determined. In the present study, ZEB1‐AS1 was found to be upregulated in IHCC cell lines and tissues. A high ZEB1‐AS1 expression was associated with clinical progression and a poor survival of patients with IHCC, and was identified as an independent risk factor for a poor prognosis. In addition, ZEB1‐AS1 promoted the proliferation and metastasis of IHCC cells both in vitro and in vivo. ZEB1‐AS1 was demonstrated to increase the expression of ZEB1 by sponging miR‐200a and to thereby accelerate epithelial‐mesenchymal transition (EMT). On the whole, the findings of the present study demonstrate that ZEB1‐AS1 promotes proliferation and metastasis in IHCC, and induces EMT through the miR‐200a/ZEB1 signaling pathway. ZEB1‐AS1 may thus be a promising prognostic biomarker and essential therapeutic target for IHCC. Introduction Intrahepatic cholangiocarcinoma (IHCC) is a rare and highly aggressive primary epithelial cancer arising from the bile duct within the liver (1). The incidence and mortality rates associated with IHCC have been continuously rising over the past decade (2). Patients are often diagnosed at an advanced incurable stage with lymph node metastasis and multicen‐ tric disease already present within the liver. Curative intent surgery is available for only 30‐40% of patients with IHCC (1). Moreover, the 5‐year survival rate is 30% even for patients who have undergone surgical resection (3) and is <5‐10% for patients with unresectable IHCC (4). The roles of adjuvant chemo‐radiotherapy and targeted therapy in IHCC have not yet been well defined and these treatments may have only modest therapeutic effects (3,5‐7). Therefore, further investi‐ gation into the mechanisms of IHCC progression is critical in order to enable the detection of novel diagnostic biomarkers and therapeutic targets. Long non‐coding RNAs (lncRNAs) are defined as tran‐ scripts greater than 200 nucleotides in length that are not translated into proteins (8). A large number of lncRNAs have been identified in recent years. lncRNAs have been reported to play critical roles in diverse cellular processes, including transcriptional regulation in cis or trans mode, the organi‐ zation of nuclear domains and the regulation of proteins or RNA molecules (9). Notably, research has suggested that lncRNAs play pivotal roles in cancer biology (10) and can act as oncogenes or tumor suppressors. Certain lncRNAs, such as MALAT1 (11), PANDA (12), H19 (13) and MEG3 (14), have been shown to be crucial regulators in a wide range of cancer types. The lncRNA ZEB1 antisense 1 (ZEB1‐AS1), an antisense transcript derived from the promoter region of ZEB1, was discovered to be upregulated in hepatocellular carcinoma by Li et al in 2015 (15). Since then, ZEB1‐AS1 has been demonstrated to be overexpressed in glioma (16), colorectal cancer (17), gastric cancer (18), prostate cancer (19) Long non‐coding RNA ZEB1‐AS1 predicts a poor prognosis and promotes cancer progression through the miR‐200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma MINGWEN JIAO1*, SHANGLEI NING2*, JINGBO CHEN3*, LILI CHEN4, MENG JIAO5, ZHONGHUI CUI3, LINGYU GUO2, WENTAO MU2 and HUI YANG3 1Department of Colorectal and Anal Surgery, Shandong Provincial Qianfoshan Hospital, Shandong University; 2Department of Hepatobiliary Surgery, Qilu Hospital of Shandong University; 3Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Shandong First Medical University; 4Department of Pathology, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250012; 5Department of Gastrointestinal Surgery, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271600, P.R. China Received October 5, 2019; Accepted February 28, 2020 DOI: 10.3892/ijo.2020.5023 Correspondence to: Dr Hui Yang, Department of Colorectal and Anal Surgery, The First Affiliated Hospital of Shandong First Medical University, 16766 Jingshi Road, Jinan, Shandong 250012,