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:
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.
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
Research background

Among common gastrointestinal malignancies, the annual incidence of pancreatic carcinoma (PC) has dramatically increased in recent years. Many studies have demonstrated that post-transcriptional regulation by long noncoding RNAs (lncRNAs) is important in PC progression. LncRNAs have emerged as pivotal molecules that participate in the initiation and progression of PC, including maintenance of cell growth, evasion of apoptosis, promotion of invasion and metastasis, maintenance of potency, and epithelial-mesenchymal transition.

Research motivation

To discover biomarkers for the diagnosis and treatment of PC.

Research objectives

To investigate the underlying mechanisms of the lncRNA DNAH17-AS1 in PC.

Research methods

LncRNA DNAH17-AS1 expression was analyzed by Western blot and reverse transcription-quantitative PCR in PC tissue and cell lines, and the clinicopathological significance of DNAH17-AS1 expression in PC patients was also investigated. In vitro experiments were performed to explore the functions of lncRNA DNAH17-AS1 in PC cells. The regulatory effects of DNAH17-AS1/miR-432-5p/PPME1 were also investigated using luciferase reporter assay, MTT assay, flow cytometry, and transwell assay.

Research results

We found that the lncRNA DNAH17-AS1 was upregulated in PC tissues and cell lines and had a significant positive relationship with degree of tumor differentiation, TNM stage, and lymph node metastasis. In vitro experiments showed that DNAH17-AS1 increased the proliferation and invasion capacity of PC cells but inhibited their apoptosis. Additionally, DNAH17-AS1 served as an oncogene in PC by downregulating miR-432-5p. Furthermore, miR-432-5p directly targeted PPME1 and normally downregulated its expression. Thus, DNAH17-AS1 increased PPME1 expression to promote PC progression.

Research conclusions

This study demonstrates that the lncRNA DNAH17-AS1 can significantly increase the growth, migration, and invasion of PC cells. DNAH17-AS1 also functions by sequestering miR-432-5p, which increases PPME1 expression and ultimately promotes PC progression. Taken together, our study provides the functional involvement of three new possible diagnostic biomarkers for PC.

Research perspectives

In the future, additional research will be carried out to further explore the important role of the lncRNA DNAH17-AS1 and whether it can be harnessed to enhance the sensitivity of PC detection and to develop novel anti-cancer treatments. The identification of the lncRNA DNAH17-AS1/miR-432-5p/PPME1 molecular axis may further provide new strategies for PC prevention and treatment.