PER1 as a Tumor Suppressor Attenuated in the Malignant Phenotypes of Breast Cancer Cells

被引：21

作者：

Liu, Yinfeng ^{[1
,2
]}

Hao, Jun ^{[3
]}

Yuan, Guanli ^{[4
]}

Wei, Mengyu ^{[1
]}

Bu, Yuhui ^{[1
]}

Jin, Tingting ^{[3
]}

Ma, Li ^{[1
]}

机构：

[1] Hebei Med Univ, Hosp 4, Dept Breast Dis Ctr, 169 Tianshan St, Shijiazhuang 050000, Hebei, Peoples R China

[2] First Hosp Qinhuangdao, Dept Breast Surg, Qinhuangdao 066000, Hebei, Peoples R China

[3] Hebei Med Univ, Inst Med & Hlth Sci, Ctr Metab Dis & Canc Res, Shijiazhuang 050000, Hebei, Peoples R China

[4] First Hosp Qinhuangdao, Dept Resp & Crit Care Med, Qinhuangdao 066000, Hebei, Peoples R China

来源：

INTERNATIONAL JOURNAL OF GENERAL MEDICINE | 2021年 / 14卷

关键词：

breast cancer; circadian clock gene; Period circadian regulator 1; PER1; tumor suppressor; CLOCK GENE PER1; DOWN-REGULATION; GROWTH;

D O I：

10.2147/IJGM.S328184

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background: Circadian clock genes play a crucial role in physiological and pathological processes, and their aberrant expressions were involved in various human cancers. The objective of this study was to investigate the expression level of Period circadian regulator 1 (PER1), an important circadian clock gene, and its biological roles in the development and progression of breast cancer. Methods: The expression level of PER1 in breast cancer samples was analyzed using the Oncomine database, and the correlation between PER1 expression and clinicopathologic para-meters was assessed by bc-GenExMiner v4.5. In addition, Kaplan-Meier plotter database was used to determine the prognostic significance of PER1 expression for breast cancer patients. The expressions of PER1 in breast cancer tissues and cells were validated by Western blot. The loss-or-gain assay of PER1 was conducted to investigate the effects of its expression on cell proliferation, migration and invasion of breast cancer. The relationship between PER1 expression and epigenetic modifications was further explored by Western blot. Results: The results of the bioinformatics analysis revealed that the expression level of PER1 was markedly reduced in breast cancer tissues (P<0.001), and patients with high expression of PER1 had a better overall survival (HR:0.78, 95% CI:0.63-0.97, P=0.026) and recurrence-free survival (HR:0.83, 95% CI:0.75-0.93, P=0.001) than those with low expression. The assay of gene loss-or-gain indicated that downregulation of PER1 expression markedly promoted cell proliferation, migration and invasion (P<0.05), whereas these malignant phenotypes of breast cancer cells were inhibited by PER1 overexpression (P<0.05). Further studies showed that trichostatin A (TSA), a histone deacetylase inhibitor, induced the expression of PER1 protein in breast cancer cells (P<0.05). Conclusion: PER1 functions as a tumor suppressor in the development and progression of breast cancer, and its expression silencing might be regulated by epigenetic modifications.

引用

页码：7077 / 7087

页数：11