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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
KLF16 promotes pancreatic adenocarcinoma cell proliferation and migration by positively regulating SMAD6
Wei Mi, Zhi Zheng, Jiong-Di Lu, Shu-Quan Duan, Jie Zhang, Hai-Qiao Zhang, Yi-Xuan Ding, Jie Yin, Feng Cao, Jun Zhang, Fei Li
Wei Mi, Zhi Zheng, Hai-Qiao Zhang, Jie Yin, Jun Zhang, Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Jiong-Di Lu, Yi-Xuan Ding, Feng Cao, Fei Li, Department of General Surgery, Xuanwu Hospital, Capital Medical University, Beijing 100053, China
Shu-Quan Duan, Department of Digestive Minimally Invasive Surgery, The Second Affiliated Hospital of Baotou Medical College, Baotou 014030, Inner Mongolia Autonomous Region, China
Jie Zhang, Department of Radiology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China
Author contributions: Mi W, Zheng Z, Lu JD, Duan SQ, Zhang J and Zhang HQ all contributed equally to this work; Mi W, Zheng Z, Lu JD and Duan SQ designed the study; Zhang HQ, Yin J and Zhang J performed the experiments; Zheng Z and Lu JD wrote the manuscript; Ding YX and Cao F performed statistical analysis; Li F and Zhang J revised the manuscript; All authors read and approved the final manuscript.
Institutional review board statement: The research was approved by the Ethics Committee of Beijing Friendship Hospital, Capital Medical University (No. 2018-P2-015-02). The principles outlined in the Declaration of Helsinki were adhered to throughout the course of this research project (as revised in 2013).
Institutional animal care and use committee statement: Every experiment that included animals was carried out in compliance with the Principles on the Protection of Experimental Animals that are outlined by the Beijing Friendship Hospital.
Conflict-of-interest statement: All authors report having no relevant conflict of interest for this article.
Data sharing statement: Data are available from the corresponding authors upon request.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Jun Zhang, MD, PhD, Chief Doctor, General Surgery Department, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xi-Cheng District, Beijing 100050, China.
zhangjun5986@ccmu.edu.cn
Received: July 15, 2022
Peer-review started: July 15, 2022
First decision: July 28, 2022
Revised: September 10, 2022
Accepted: October 18, 2022
Article in press: October 18, 2022
Published online: November 15, 2022
Processing time: 122 Days and 20.3 Hours
BACKGROUND
Pancreatic adenocarcinoma (PAAD) is a cancerous tumor with an extremely poor 5-year survival rate. The exploration of biomarkers for the diagnosis and treatment of PAAD is crucial in clinical practice. Krüppel-like factors (KLFs) are involved in a variety of biological functions in cells. According to multiple studies, KLF16 behave as an oncogene in prostate, breast and gastric cancers. However, no research has been done on the significance of KLF16 in PAAD.
AIM
To explore the molecular mechanisms of KLF16 in PAAD.
METHODS
KLF16 was identified in the tumor specimens and normal tissues by GEPIA database and verified by quantitative real-time PCR (qRT-PCR). Knockdown or exogenous expression of KLF16, combined with in vitro and in vivo assays, was performed to show the functional significance of KLF16. The molecular mechanism of KLF16 was demonstrated by qRT-PCR, western blotting, immunoprecipitation assay and flow cytometry.
RESULTS
We showed that KLF16 was highly expressed in PAAD patients based on the GEPIA database. KLF16 silencing suppressed while KLF16 overexpression promoted the malignant function of PAAD cells. Based on RNA sequencing, we discovered that KLF16 potentiated the expression of SMAD6 in PAAD cells. SMAD6 transcript abundance was increased and positively correlated with KLF16 expression in PAAD samples. In addition, inhibiting SMAD6 was able to mitigate the effects of KLF16 overexpression on PAAD cell processes, suggesting the importance of SMAD6 in the development of KLF16-triggered PAAD.
CONCLUSION
KLF16/SMAD6 axis might be explored as a therapeutic target for PAAD therapy.
Core Tip: Our study provided the evidence that KLF16 acted as an oncogene in pancreatic adenocarcinoma (PAAD). We also identified that SMAD6 served as the downstream substrate of KLF16 and this signaling cascade has never been reported. This mechanism indicated a novel insight into the pathological events during the development of PAAD.
