Case Control Study
Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Dec 14, 2019; 25(46): 6728-6742
Published online Dec 14, 2019. doi: 10.3748/wjg.v25.i46.6728
Long non-coding RNA HULC as a diagnostic and prognostic marker of pancreatic cancer
Zheng-Lin Ou, Zhen Luo, Ye-Bin Lu
Zheng-Lin Ou, Zhen Luo, Ye-Bin Lu, Department of General Surgery, Xiangya Hospital, Central South University, Changsha 410008, Hunan Province, China
Author contributions: Ou ZL designed the research; Lu YB performed the research; Luo Z contributed new reagents and analytic tools; Lu YB analyzed the data; Luo Z wrote the paper.
Supported by the Hunan Natural Science Youth Foundation, No. 2017JJ3508.
Institutional review board statement: The study was authorized by the Ethics Committee of Xiangya Hospital, Central South University.
Informed consent statement: All patients gave informed consent.
Conflict-of-interest statement: There was no competing interest.
Data sharing statement: All the data in the current research are available from the corresponding author on reasonable request.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Ye-Bin Lu, MD, Doctor, Department of General Surgery, Xiangya Hospital, Central South University, No.87, Xiang Ya Road, Changsha 410008, Hunan Province, China. luyebin6@sina.com
Telephone: +86-0731-89753009 Fax: +86-0731-89753009
Received: September 24, 2019
Peer-review started: September 24, 2019
First decision: November 4, 2019
Revised: November 18, 2019
Accepted: November 29, 2019
Article in press: November 29, 2019
Published online: December 14, 2019
Processing time: 81 Days and 4.2 Hours
Abstract
BACKGROUND

Long non-coding RNA (lncRNA) is abnormally expressed in various malignant tumors. In recent years, it has been found that IncRNA HULC is increasingly expressed in pancreatic cancer tissues and is involved in the development and progression of pancreatic cancer. However, the clinical value of serum HULC in pancreatic cancer remains unclear, and there are few studies on how HULC regulates the biological function of pancreatic cancer cells.

AIM

To determine the value of lncRNA HULC in the diagnosis and prognosis of pancreatic cancer, and its possible biological potential.

METHODS

Sixty patients with pancreatic cancer and sixty patients with benign pancreatic diseases admitted to Xiangya Hospital, Central South University were assigned to the pancreatic cancer group and the benign disease group, respectively, and another 60 healthy subjects were enrolled as the normal group during the same period. HULC-siRNA and NC-siRNA were transfected into pancreatic cancer cells. Quantitative real-time polymerase chain reaction was performed to determine the expression of HULC in tissues, serum, and cells. Western Blot was carried out to determine the expression of β-catenin, c-myc, and cyclin D1 in cells, and the cell counting kit-8, flow cytometry, and Transwell assay were conducted to determine the proliferation, apoptosis and invasion of cells.

RESULTS

Highly expressed in the tissues and serum of pancreatic cancer patients, HULC showed good clinical value in distinguishing between patients with pancreatic cancer, patients with benign pancreatic diseases and healthy subjects. HULC was related to pathological parameters including tumor size, T staging, M staging and vascular invasion, and the area-under-the-curve for evaluating these four parameters was 0.844, 0.834, 0.928 and 0.818, respectively. Patients with low expression of HULC had a significantly higher 3-year overall survival (OS) and 5-year OS than those with high expression. T staging, M staging, vascular invasion, and HULC were independent prognostic factors affecting the 3-year OS of patients with pancreatic cancer. Inhibition of HULC expression prevented the proliferation and invasion of pancreatic cancer cells, promoted apoptosis, and inhibited the expression of Wnt/β-catenin signaling pathway-related proteins, β-catenin, c-myc, and cyclin D1. The Wnt/β-catenin signaling pathway agonist (LiCl) restored proliferation, apoptosis, and invasion of pancreatic cancer cells with inhibited expression of HULC.

CONCLUSION

HULC is an effective marker for the diagnosis and prognosis of pancreatic cancer, which may affect the biological function of pancreatic cancer cells through the Wnt/β-catenin signaling pathway.

Keywords: Long non-coding RNA HULC; Diagnosis; Prognosis; Pancreatic cancer; Wnt/β-catenin signaling pathway; Biological function

Core tip: In this study, we evaluated the role of HULC in the diagnosis and prognosis of pancreatic cancer and its possible biological potential. Firstly, we studied the expression of HULC in the serum and tissues of patients with pancreatic cancer. Secondly, we analyzed the relationship between HULC and the clinical pathological parameters and prognosis of patients. Finally, we determined the effects of inhibiting HULC expression on the proliferation, apoptosis and invasion of pancreatic cancer cells and its possible biological potential.