Dataset Information

Long non?coding RNA ZEB1?AS1 predicts a poor prognosis and promotes cancer progression through the miR?200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma.

ABSTRACT: 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.

SUBMITTER: Jiao M

PROVIDER: S-EPMC7170034 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Long non‑coding RNA ZEB1‑AS1 predicts a poor prognosis and promotes cancer progression through the miR‑200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma.

Jiao Mingwen M Ning Shanglei S Chen Jingbo J Chen Lili L Jiao Meng M Cui Zhonghui Z Guo Lingyu L Mu Wentao W Yang Hui H

International journal of oncology 20200320 6

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 ...[more]

PMID: 32236578

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Project description:Background & aimsIntrahepatic cholangiocarcinoma (iCCA) is a deadly cancer worldwide with an increasing incidence and limited therapeutic options. Therefore, there is an urgent need to open the field to new concepts for identifying clinically relevant therapeutic targets and biomarkers. Here, we explored the role and the clinical relevance of circular RNA (circRNA) circLTBP2 in iCCA.MethodsTransforming growth factor β (TGFβ)-regulated circRNAs were identified by dedicated microarrays in human HuCC-T1 iCCA cell line, and their clinical relevance was evaluated in independent cohorts of patients. Gain and loss of function of circLTBP2 combined with functional tests was performed in vitro and in vivo in mice. RNA pulldown, microRNA sequencing, and RNA immunoprecipitation were performed to explore the sponging activity of circLTBP2.ResultsCircLTBP2 (has_circ_0032603) was identified as a novel TGFβ-induced circRNA in several cholangiocarcinoma cell lines. CircLTBP2 promotes tumour cell proliferation, migration, and resistance to gemcitabine-induced apoptosis in vitro and tumour growth in vivo. Mechanistically, circLTBP2 acts as a competitive RNA regulating notably the activity of the tumour suppressor microRNA miR-338-3p, leading to the overexpression of its pro-metastatic targets. The restoration of miR-338-3p levels in iCCA cells reversed the pro-tumourigenic effects driven by circLTBP2, including the resistance to gemcitabine-induced apoptosis. In addition, circLTBP2 expression predicted a reduced survival, as detected in not only tumour tissues but also serum extracellular vesicles isolated from patients with iCCA.ConclusionsCircLTBP2 is a novel effector of the pro-tumourigenic arm of TGFβ and a clinically relevant biomarker easily detected from liquid biopsies in iCCA.Impact and implicationsIntrahepatic cholangiocarcinoma (iCCA) is an aggressive cancer with limited therapeutic options. Opening the field to new concepts is urgently needed to improve the survival of patients. Here, we evaluated the role and the clinical relevance of circular RNA. We report that TGFβ-induced circLTBP2 contributes to CCA carcinogenesis and may constitute a clinically relevant prognostic biomarker detected in liquid biopsies.

Dataset Information

Long non?coding RNA ZEB1?AS1 predicts a poor prognosis and promotes cancer progression through the miR?200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma.

Publications

Long non‑coding RNA ZEB1‑AS1 predicts a poor prognosis and promotes cancer progression through the miR‑200a/ZEB1 signaling pathway in intrahepatic cholangiocarcinoma.

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