Case Control Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Nov 15, 2020; 12(11): 1272-1287
Published online Nov 15, 2020. doi: 10.4251/wjgo.v12.i11.1272
LncRNA C9orf139 can regulate the growth of pancreatic cancer by mediating the miR-663a/Sox12 axis
Jin-Nian Ge, Di Yan, Chun-Lin Ge, Min-Jie Wei
Jin-Nian Ge, Chun-Lin Ge, Department of General Surgery, The First Affiliated Hospital of China Medical University, Shenyang 110001, Liaoning Province, China
Di Yan, Intensive Care Unit, The Central Affiliated Hospital of Shenyang Medical College, Shenyang 110024, Liaoning Province, China
Min-Jie Wei, Department of Pharmacology, School of Pharmacy, China Medical University, Shenyang 110122, Liaoning Province, China
Author contributions: Ge JN and Yan D contributed to the study design and reviewed the manuscript; Ge CL and Wei MJ analyzed the data and wrote the manuscript; Yan D contributed to the data collection, data interpretation, and manuscript writing; and all authors read and approved the final manuscript.
Institutional review board statement: The study was reviewed and approved for publication by the First Affiliated Hospital of China Medical University.
Informed consent statement: All study participants or their legal guardian provided informed written consent about personal and medical data collection prior to study enrollment.
Conflict-of-interest statement: All the authors have no conflict of interest related to the manuscript.
Data sharing statement: No additional data are available.
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 that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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: Min-Jie Wei, PhD, Doctor, Department of Pharmacology, School of Pharmacy, China Medical University, No. 155 Nanjing North Street, Heping District, Shenyang 110122, Liaoning Province, China. weiminjie112233@163.com
Received: June 1, 2020
Peer-review started: June 1, 2020
First decision: September 11, 2020
Revised: September 24, 2020
Accepted: October 12, 2020
Article in press: October 12, 2020
Published online: November 15, 2020
Abstract
BACKGROUND

Recent studies have proved the important role of many oncogenic long non-coding RNAs (lncRNAs) in the progression of pancreatic cancer, but little is known about the mechanisms of tumor suppression in pancreatic cancer.

AIM

To evaluate the function of tumor suppressor lncRNA C9orf139 in pancreatic cancer progression and to study the underlying mechanism.

METHODS

We assigned 54 patients with pancreatic ductal adenocarcinoma treated at our hospital to the patient group and 30 normal subjects undergoing physical examination to the control group. RT-qPCR was used to measure the relative expression of C9orf139 in the tissue and serum of patients, in an attempt to investigate the prognostic value of C9orf139 in pancreatic cancer patients. The luciferase reporter gene assay was performed to determine the interaction between C9orf139 and miR-663a. The biological function of C9orf139 was assessed by in vitro assays and in vivo subcutaneous tumor formation tests in animal models. To figure out the molecular mechanism of C9orf139 to act on miR-663a/Sox12, RNA pull-down, Western blot assay, RNA immunoprecipitation assay, and co-immunoprecipitation assay were performed.

RESULTS

C9orf139 level significantly increased in the tissue and serum of patients, which had clinical diagnostic value for pancreatic cancer. Patients with high C9orf139 expression had a higher risk of progressing to stage III + IV, lymph node metastasis, and poor differentiation. Cox regression analysis suggested that C9orf139, tumor-node-metastasis stage, and lymph node metastasis were independent prognostic factors in patients. The underlying mechanism of C9orf139 was that it promoted the growth of pancreatic cancer cells by modulating the miR-663a/Sox12 axis.

CONCLUSION

C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663a/Sox12 axis.

Keywords: C9orf139, miR-663a, Sox12, Pancreatic cancer, Prognosis, Tumor formation in nude mice

Core Tip: C9orf139 is highly expressed in pancreatic cancer, qualified to be used as a potential diagnostic and prognostic marker for pancreatic cancer. Its promotion of pancreatic cancer cell growth is achieved by mediating the miR-663a/Sox12 axis.