Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 21, 2020; 26(15): 1745-1757
Published online Apr 21, 2020. doi: 10.3748/wjg.v26.i15.1745
DNAH17-AS1 promotes pancreatic carcinoma by increasing PPME1 expression via inhibition of miR-432-5p
Tao Xu, Ting Lei, Si-Qiao Li, Er-Hui Mai, Fei-Hu Ding, Bin Niu
Tao Xu, Ting Lei, Si-Qiao Li, Er-Hui Mai, Fei-Hu Ding, Department of Hepatobiliary Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, Luoyang 471000, Henan Province, China
Bin Niu, Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, Guangdong Province, China
Author contributions: Niu B designed the research, supervised the study, and provided critical feedback at all stages; Xu T analyzed the data and wrote the paper; Xu T, Lei T, Li SQ, Mai EH, and Ding FH performed the research.
Institutional review board statement: This study was reviewed and approved by the Human Ethics Committee of Luoyang Central Hospital Affiliated to Zhengzhou University.
Conflict-of-interest statement: The authors declare no conflict of interest.
Data sharing statement: No additional data are available.
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: Bin Niu, PhD, Doctor, Department of Gastrointestinal Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, 52 Meihua East Road, Xiangzhou District, Zhuhai 519000, Guangdong Province, China. nongmunnl125@163.com
Received: December 16, 2019
Peer-review started: December 16, 2019
First decision: January 19, 2020
Revised: February 7, 2020
Accepted: March 19, 2020
Article in press: March 19, 2020
Published online: April 21, 2020
Processing time: 127 Days and 2.6 Hours
Abstract
BACKGROUND

The incidence and mortality rates of pancreatic carcinoma (PC) are rapidly increasing worldwide. Long noncoding RNAs (lncRNAs) play critical roles during PC initiation and progression. Since the lncRNA DNAH17-AS1 is highly expressed in PC, the regulation of DNAH17-AS1 in PC was investigated in this study.

AIM

To investigate the expression and molecular action of lncRNA DNAH17-AS1 in PC cells.

METHODS

The PC expression data for the lncRNA DNAH17-AS1 was downloaded from The Cancer Genome Atlas database and used to examine its profile. Western blot and reverse transcription-quantitative PCR were employed to assess protein and mRNA expression. A subcellular fractionation assay was used to determine the location of DNAH17-AS1 in cells. In addition, the regulatory effects of DNAH17-AS1 on miR-432-5p, PPME1, and tumor activity were investigated using luciferase reporter assay, MTT viability analysis, flow cytometry, and transwell migration analysis.

RESULTS

DNAH17-AS1 was upregulated in PC cells and was associated with aggressive tumor behavior and poor prognosis for patients. Silencing DNAH17-AS1 promoted the apoptosis and reduced the viability, invasion, and migration of PC cells. In addition, DNAH17-AS1 served as a PC oncogene by downregulating miR-432-5p which normally directly targeted PPME1 to downregulate its expression.

CONLUSION

DNAH17-AS1 functions in PC as a tumor promoter by regulating the miR-432-5p/PPME1 axis. This finding may provide new insights for PC prognosis and therapy.

Keywords: Long noncoding RNAs; DNAH17-AS1; Pancreatic carcinoma; MiR-432-5p; PPME1; Molecular mechanism

Core tip: DNAH17-AS1 is upregulated in pancreatic carcinoma (PC) and is associated with aggressive clinical presentation in PC patients. DNAH17-AS1 promotes PC cell viability, invasion, and migration, and its silencing promotes PC cell apoptosis. DNAH17-AS1 is found primarily in the cytoplasm and participates in the competing endogenous RNA regulatory network. DNAH17-AS1 functions as a tumor promoter in PC by downregulating miR-432-5p and upregulating PPME1.