Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 25, Issue 7, Pages 3226-3238Publisher
WILEY
DOI: 10.1111/jcmm.16392
Keywords
cholangiocarcinoma; circ‐ LAMP1; circRNA; miR‐ 556‐ 5p; miR‐ 567; YY1
Categories
Funding
- Postgraduate Innovative Research Project of Harbin Medical University [YJSCX2016-21HYD]
- Outstanding Youth Project of Natural Science Foundation of Heilongjiang [YQ2019H007]
- Hong Kong Scholars Program [XJ2020012]
- Special Project of China Postdoctoral Science Foundation [2019T120279]
- Fundamental Research Funds for the Heilongjiang Provincial Universities [2018-KYYWF-0498, 2018-KYYWF-0511]
- China Postdoctoral Science Foundation [2018M640311, 2018M641849]
- Special Project of Heilongjiang Postdoctoral Science Foundation [LBH-TZ1016]
- Foundation of Key Laboratory of Myocardial Ischemia, Ministry of Education [KF201810]
- Heilongjiang Provincial Postdoctoral Science Foundation [LBH-Z18107, LBH-Z18112]
- Chen Xiaoping Foundation for the Development of Science and Technology of Hubei Province [CXPJJH11800004-001]
- National Natural Science Foundation of China [81902431]
- Natural Science Foundation of Heilongjiang Province [D201239]
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The up-regulation of circ-LAMP1 in cholangiocarcinoma tissues and cell lines is associated with clinical severity, high post-operative recurrence, and poor prognosis. Circ-LAMP1 plays an oncogenic role in mediating cell growth, apoptosis, migration, and invasion, partially dependent on its modulation of YY1. This study suggests that circ-LAMP1 may serve as a promising biomarker/therapeutic target for cholangiocarcinoma.
Dysregulation of circular RNAs (circRNAs) executes important regulatory roles in carcinogenesis. Nonetheless, few studies focused on the mechanisms of circRNAs in cholangiocarcinoma (CCA). qRT-PCR was applied to verify the dysregulated circRNAs in CCA. Fisher's exact test, Kaplan-Meier analysis and Cox regression model were utilized to investigate the clinical implications of circ-LAMP1 in the patients with CCA. The viability, apoptosis, migration and invasion of CCA cells were detected after silencing/overexpression of circ-LAMP1. Xenograft and lung metastasis assays were performed to verify the in vitro results. The regulatory networks of circ-LAMP1 were unveiled by bioinformatic analysis, RNA immunoprecipitation (RIP), RNA pulldown and luciferase reporter assays. Up-regulation of circ-LAMP1 was found in CCA tissue samples and cell lines. Enhanced level of circ-LAMP1 was linked to clinical severity, high post-operative recurrence and poor prognosis for the patients with CCA. Gain/loss-of-function assays confirmed the oncogenic role of circ-LAMP1 in mediating cell growth, apoptosis, migration and invasion. Nevertheless, the level of circ-LAMP1 had no effect on normal biliary epithelium proliferation and apoptosis. Animal study further verified the in vitro data. Mechanistically, circ-LAMP1 directly sponged miR-556-5p and miR-567, thereby releasing their suppression on YY1 at post-transcriptional level. Rescue assay indicated that the oncogenic role of circ-LAMP1 is partially dependent on its modulation of YY1 in CCA. In summary, this study suggested that circ-LAMP1 might be used as a promising biomarker/therapeutic target for CCA.
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