• J Chin Med Assoc · Nov 2022

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

    • Yinfeng Liu, Zizheng Wu, Yanli Li, Jing Zhang, Yang Gao, Guanli Yuan, and Meng Han.
    • Department of Breast Surgery, The First Hospital of Qinhuangdao, Qinhuangdao, Hebei, China.
    • J Chin Med Assoc. 2022 Nov 1; 85 (11): 105110601051-1060.

    BackgroundThe 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.MethodsPER3-silencing and PER3-overexpression cell lines were established by transfecting with pGenesil1-PER3 and Lenti-blast-PER3 vector, respectively.ResultsThe 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.ConclusionThese 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.Copyright © 2022, the Chinese Medical Association.

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