Subcellular localization of nucleolar protein 14 and its proliferative function mediated by miR-17-5p and E2F4 in pancreatic cancer

Sep 24, 2026

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Pancreatic cancer is described as a highly lethal malignancy, where limitless proliferative ability drives tumorigenesis. The study focuses on NOP14, a ribosome biogenesis protein, and clarifies its role and molecular mechanism in human pancreatic cancer. Using quantitative assays, NOP14 localization is evaluated and found mainly in the nucleolus. Functional experiments show NOP14 promotes proliferation in vitro, and miR-17-5p is identified as a downstream target regulating P130. NOP14 also increases E2F4 expression independently, activating genes such as CCNE1, PIM1, and AKT1 to further enhance proliferation, providing insight for targeted therapy.

LanguageEnglish

CategoryHealthcare

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ABSTRACT

INTRODUCTION

RESULTS

Subcellular localization of NOP14 in pancreatic cancer cells

[www.aging-us.com](www.aging-us.com) AGING 2023, Vol. 15, No. 14 Research Paper Subcellular localization of nucleolar protein 14 and its proliferative function mediated by miR-17-5p and E2F4 in pancreatic cancer Yong-Xing Du1,*, Ying Zhou2,*, Xiao-Hao Zheng1,*, Yun-Jie Duan1, Zong-Ting Gu1, Ye-Feng Yin3,*, Cheng-Feng Wang1,4,* 1 Department of Pancreatic and Gastric Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China 2 Department of Endocrinology, China-Japan Friendship Hospital, Beijing 100029, People’s Republic of China 3 Department of Colorectal Surgery, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, People’s Republic of China 4Shanxi Province Cancer Hospital/ Shanxi Hospital Affiliated to Cancer Hospital, Chinese Academy of Medical Sciences/Cancer Hospital Affiliated to Shanxi Medical University, Taiyuan 030013, Shanxi, People’s Republic of China * Equal contribution Correspondence to: Ye-Feng Yin, Cheng-Feng Wang; email: [yefeng541009@163.com](yefeng541009@163.com), [https://orcid.org/0000-0002-3182-](https://orcid.org/0000-0002-3182-)[ ](https://orcid.org/0000-0002-3182-)004X; [wangchengfeng@cicams.ac.cn](wangchengfeng@cicams.ac.cn) Keywords: pancreatic cancer, nucleolar protein 14, subcellular localization, miR17-5p, E2F4 Received: November 12, 2022 Accepted: June 22, 2023 Published: July 27, 2023 Copyright: © 2023 Du et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Pancreatic cancer is one of the most lethal malignancies worldwide. Acquiring infinite proliferation ability is a key hallmark and basis of tumorigenesis. NOP14 is an identified ribosome biogenesis protein that plays potential roles in cell proliferation. However, the function and molecular mechanism of NOP14 remain ambiguous in most human cancers. In this study, we first investigated the subcellular localization and expression of NOP14 by multiple quantitative assays in pancreatic cancer. We confirmed that NOP14 was mainly localized in nucleolus inhuman pancreatic cancer cells. Then we studied the regulatory effects of this nucleolus protein on tumor cell proliferation in vitro. NOP14 was demonstrated to play a dominant pro-proliferation role in pancreatic cancer. Furthermore, we identified miR17-5p as a downstream target of NOP14. Transfection of miR17-5p mimics or inhibitors rescued the down- or upregulated effect of NOP14 on cell proliferation by regulating expression of P130. In addition, NOP14 induced expression of transcription factor E2F4 independent of miR17-5p/P130 signaling, which simultaneously activated a set of targeted genes, such as CCNE1, PIM1, AKT1 etc., to promote tumor proliferation. These findings might provide novel insights for better understanding the diverse function of NOP14 in human malignancies to develop new strategies for targeted therapy. INTRODUCTION Pancreatic adenocarcinoma (PDAC) ranks the fourth leading cause of death in human malignancies [1] . Due to its insidious onset, rapid progression, and resistance to most current therapies, including radiotherapy, chemotherapy and targeted immunotherapy, the prognosis of patients with PDAC has not being improved significantly for decades. Moreover, PDAC is expected to become the second lethal cancer up to 2030 with annually increasing incidence and mortality [2, 3] . Therefore, it is urgent to develop new therapeutic targets or biomarkers to improve the current clinical dilemma. In humans, the nuclear protein 14 (NOP14) gene is located on chromosome 4p16.317 . Previous studies have shown that NOP14 participates in ribosome biosynthesis by affecting the

FAQs

Where is nucleolar protein 14 (NOP14) mainly localized in pancreatic cancer cells?

NOP14 is mainly localized in the nucleolus in pancreatic cancer cells based on immunofluorescence and nuclear-cytoplasmic separation assays, and also supported by immunohistochemistry in tissues.

How does NOP14 affect pancreatic cancer cell proliferation?

NOP14 is demonstrated to play a dominant pro-proliferation role in pancreatic cancer, with functional assays showing that altering NOP14 levels changes proliferation accordingly.

What is the relationship between NOP14, miR-17-5p, and P130?

miR-17-5p is identified as a downstream target of NOP14. Transfection with miR-17-5p mimics or inhibitors rescues the down- or upregulated effects of NOP14 on proliferation by regulating P130 expression.

Sep 24, 2026

Uploaded by Angel