PER3 plays anticancer roles in the oncogenesis and progression of breast cancer via regulating MEK/ERK signaling pathway

Q: What was the study’s main goal regarding PER3 in breast cancer?

To investigate PER3 expression and determine its biological function in breast cancer, focusing on mechanisms related to MEK/ERK signaling.

Q: How were PER3-silencing and PER3-overexpression cell models established?

By transfecting cells with pGenesil1-PER3 for PER3 silencing and Lentiblast-PER3 for PER3 overexpression.

Q: What relationship did PER3 show with MEK/ERK signaling and cancer phenotypes?

PER3 knockdown decreased p-MEK and p-ERK1/2 and promoted malignant behaviors, while PER3 overexpression inhibited these phenotypes. PD98059 suppressed PER3-silencing effects, and TPA reversed the inhibitory effects of PER3 overexpression.

Sep 29, 2026

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Background: Explore expression and biological function of period circadian regulator 3 (PER3), a core circadian clock gene, in breast cancer. Methods: PER3-silencing and PER3-overexpression cell lines were generated using pGenesil1-PER3 and Lentiblast-PER3 vectors. Results: PER3 was downregulated in breast cancer tissues and cell lines, with low levels linked to advanced tumor and T stages. PER3 knockdown promoted proliferation, invasion, and metastasis in vitro, while overexpression inhibited malignant phenotypes. PER3 modulated MEK/ERK signaling, and MEK/ERK inhibitor PD98059 or activator TPA reversed corresponding effects. Conclusion: PER3 acts as a tumor suppressor, with anticancer effects dependent on MEK/ERK pathway.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Abstract

1. INTRODUCTION

J Chin MedAssoc Original article PER3 plays anticancer roles in the oncogenesisand progression of breast cancer via regulating MEK/ERK signaling pathway Yinfeng Liua, Zizheng Wua, Yanli Lib, Jing Zhangb, Yang Gaoc, Guanli Yuand,* , Meng Hana,* aDepartment of Breast Surgery, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China; bDepartment of Orthopedics, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China; cDepartment of Intensive Care Unit, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China; dDepartment of Respiratory and Critical Care Medicine, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China Abstract Background: The study aimed at exploring the expression of period circadian regulator 3 (PER3), a major member of the circadian clock gene family, and its biological function in breast cancer. Methods: PER3-silencing and PER3-overexpression cell lines were established by transfecting with pGenesil1-PER3 and Lentiblast-PER3 vector, respectively. Results: The results showed that the expression of PER3 was downregulated in breast cancer tissues and cell lines (p < 0.001), and its low expression was significantly correlated with advanced tumor stage (p = 0 .031) and advanced T stage (p = 0 .018) . Cell functional experiments indicated that the silencing of PER3 elevated the ability of breast cancer cells to proliferate, invade, and metastasize in vitro (p < 0.05), whereas overexpression of PER3 had an inhibitory effect on these malignant phenotype of breast cancer cells (p < 0.05) . Moreover, the activation of MEK/ERK signaling pathway was evidently inhibited by silencing of PER3, as evidenced by decreased expression levels of p-MEK and p-ERK1/2 proteins in breast cancer cells (p < 0 .05) . PER3-silencing and PER3-overexpression cells were treated with PD98059 (an inhibitor of MEK/ERK signaling) and TPA (an activator of MEK/ERK signaling), respectively. It was observed that PER3 silencing-mediated malignant phenotype in breast cancer cells was markedly suppressed by PD98059 treatment. Instead, TPA exposure reversed the inhibitory effects of PER3 overexpression on DNA synthesis, proliferation, migration, and invasion of breast cancer cells. Conclusion: These findings suggested that PER3 function as a tumor suppressor in the development and progression of breast cancer and its anticancer roles might be dependent on the MEK/ERK signaling pathway. Keywords: Anticancer; Breast cancer; MEK/ERK signaling; Period circadian regulator 3; Tumor suppressor 1. INTRODUCTION Recent cancer statistics have shown that breast cancer is the most frequently diagnosed malignancy among females around the world, and it is characterized by highly molecular and histological heterogeneity.1–3 Despite the substantial progress in diagnostic and therapeutic methods, high rates of loco-regional recurrence and distant metastasis are still great challenges for clinical treatment of breast cancer patients.4,5 The lack of effective * Address correspondence. Dr. Guanli Yuan, Department of Respiratory and Critical Care Medicine, The First Hospital of Qinhuangdao, 258, Wenhua Road, Haigang District, Qinhuangdao 066500, Hebei, China. E-mail address: [yuanguanli6_med@126.com](yuanguanli6_med@126.com) (G. Yuan); Dr. Meng Han, Department of Breast Surgery, The First Hospital of Qinhuangdao, 258, Wenhua Road, Haigang District, Qinhuangdao 066500, Hebei, [China. E-mail address: meng68527@126.com](China. E-mail address: meng68527@126.com) (M. Han). Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article. Journal of Chinese Medical Association. (2022) 85: 1051-1060. Received May 1, 2022; accepted June 19, 2022. doi: 10. 1097/JCMA.0000000000000781. Copyright © 2022, the Chinese Medical Association. This is an open access article under the CC BY-NC-ND license ([http://creativecommons.org/licenses/](http://cre

FAQs

What was the study’s main goal regarding PER3 in breast cancer?

To investigate PER3 expression and determine its biological function in breast cancer, focusing on mechanisms related to MEK/ERK signaling.

How were PER3-silencing and PER3-overexpression cell models established?

By transfecting cells with pGenesil1-PER3 for PER3 silencing and Lentiblast-PER3 for PER3 overexpression.

What relationship did PER3 show with MEK/ERK signaling and cancer phenotypes?

PER3 knockdown decreased p-MEK and p-ERK1/2 and promoted malignant behaviors, while PER3 overexpression inhibited these phenotypes. PD98059 suppressed PER3-silencing effects, and TPA reversed the inhibitory effects of PER3 overexpression.

Sep 29, 2026

Upload by Jacob