|
|||||
|
|
Circ-LAMP1 contributes to the growth and metastasis of cholangiocarcinoma via miR-556-5p and miR-567 mediated YY1 activation |
|
| Authors: | Yi Xu Ping Gao Zhidong Wang Zhilei Su Guanqun Liao Yi Han Yifeng Cui Yue Yao Xiangyu Zhong |
| Affiliation: | 1. Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China Young Scholar of General Surgery Climbing Program of China, China Contribution: Funding acquisition (equal), Investigation (equal), Methodology (equal);2. Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin, China Contribution: Data curation (equal), Formal analysis (equal), Investigation (equal);3. Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China Contribution: Formal analysis (equal), Investigation (equal), Software (equal), Visualization (equal), Writing - original draft (equal);4. Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China Contribution: Investigation (equal), Validation (equal), Writing - review & editing (equal);5. Department of Interventional Radiology, Stanford University School of Medicine, Stanford, CA, USA Contribution: Investigation (equal);6. Department for Visceral, Thoracic and Vascular Surgery at the University Hospital, Technical University Dresden, Dresden, Germany Contribution: Investigation (equal);7. Department of Hepatic Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, China;8. Department of Endocrinology and Metabolism, Second Affiliated Hospital of Harbin Medical University, Harbin, China;9. Department of Hepatopancreatobiliary Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, China |
| Abstract: | 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. |
| Keywords: | cholangiocarcinoma circ-LAMP1 circRNA miR-556-5p miR-567 YY1 |