Basic Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Oncol. Jul 15, 2025; 17(7): 108274
Published online Jul 15, 2025. doi: 10.4251/wjgo.v17.i7.108274
BTNL9 exerts anti-cancer effects by inhibiting CDC20 to induce G2/M arrest in pancreatic cancer
Mao Xiao, Zhi-Yan Luo, Ai-Ru Yu, Ke Xu, Wei Zhou
Mao Xiao, Department of Respiratory Medicine, Second People’s Hospital of Xindu Distrct, Chengdu 610501, Sichuan Province, China
Zhi-Yan Luo, Department of Emergency, Second People’s Hospital of Xindu Distrct, Chengdu 610501, Sichuan Province, China
Ai-Ru Yu, Ke Xu, Wei Zhou, School of Clinical Medicine, Chengdu Medical College, Chengdu 610500, Sichuan Province, China
Ke Xu, Department of Oncology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
Wei Zhou, Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, Chengdu 610500, Sichuan Province, China
Co-corresponding authors: Ke Xu and Wei Zhou.
Author contributions: Xu K and Zhou W contributed equally to this study as co-corresponding authors; Xu K and Zhou W were responsible for conception and design, for administrative, technical, or material support, and for study supervision; Xiao M and Luo ZY were responsible for methodology; Xu K and Yu AR were responsible for acquisition of data; Xiao M and Luo ZY were responsible for analysis and interpretation of data; Xiao M, Luo ZY, Yu AR, Xu K, and Zhou W were responsible for writing, reviewing, and/or revising the manuscript; All authors were responsible for final approval.
Supported by Sichuan Medical Association Research Project, No. Q2024049; Clinical Science Research Fund of Chengdu Medical College, No. 24 LHLNYX1-03; Chengdu Medical College Elite Peak Program, No. 2024qnGzn04; and Key Clinical Specialty of Sichuan Province, No. YS00109.
Institutional review board statement: Our study was approved by Ethics Committee of the First Affiliated Hospital of Chengdu Medical College (No. 2022CYFYIRB-SQ-22).
Conflict-of-interest statement: The authors declare no potential conflicts of interest.
Data sharing statement: The data that supports the findings of this study are available from the corresponding author upon reasonable request.
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: Wei Zhou, MD, Research Assistant Professor, Department of Radiology, The First Affiliated Hospital of Chengdu Medical College, No. 278 Baoguang Street, Xindu District, Chengdu 610500, Sichuan Province, China. zhouwei@cmc.edu.cn
Received: April 10, 2025
Revised: May 1, 2025
Accepted: May 29, 2025
Published online: July 15, 2025
Processing time: 96 Days and 7 Hours
Abstract
BACKGROUND

Pancreatic cancer (PC) is an aggressive malignancy. As a member of the BTN/BTNL family, BTNL9 has been identified as a tumor suppressor in breast cancer, lung adenocarcinoma, and colon cancer; however, its role and underlying mechanisms in PC remain to be elucidated.

AIM

To investigate the role of BTNL9 in the pathogenesis and development of PC.

METHODS

The difference of BTNL9 expression in cancer and adjacent normal tissues was analyzed by RNA sequencing data from a public database and tissue microarray detection. The relationship between BTNL9 expression and the prognosis of patients was also studied. The effects of BTNL9 on proliferation, metastasis, and cell cycle of PC cells were investigated by phenotypic experiments. The mechanism was investigated by RNA sequencing, western blotting, and immunofluorescence detection.

RESULTS

The mRNA and protein levels of BTNL9 in PC tissues were downregulated compared with normal tissues. Based on survival data from The Cancer Genome Atlas and tissue microarray, BTNL9 was an independent influencing factor for overall survival, and its low expression predicted a shortened overall survival of patients. In vitro, BTNL9 could inhibit cell proliferation and metastasis in both PANC-1 and MIA PaCa-2 cells and induce cell cycle arrest in G2/M phases. Downregulation of BTNL9 could activate the cell cycle signaling pathway. Furthermore, overexpression of BTNL9 could significantly inhibit the expression of cell division cycle 20 (CDC20). Rescue experiments demonstrated that overexpression of CDC20 reversed the effect of BTNL9 on the proliferation, metastasis, and cell cycle of PC cells.

CONCLUSION

The expression of BTNL9 was downregulated in PC, and it has the prediction ability for prognosis. Functionally, BTNL9 exerted an anti-cancer effect by suppressing downstream CDC20 expression in PC.

Keywords: Pancreatic cancer; Butyrophilin like 9; Cell division cycle 20; Cell cycle; Prognosis

Core Tip: The present study reported the downregulated expression of BTNL9 in pancreatic cancer and correlated with a poorer prognosis. Pancreatic cancer cells overexpressing BTNL9 exhibited cell cycle arrest at G2/M, accompanied by a reduction in their proliferative and metastatic capacity. BTNL9 regulated the cell cycle by inhibiting cell division cycle 20.