The impaction of clock-knockdown on autophagy in 4T1 breast cancer cells

ABSTRACT

Circadian rhythm has been involved in the regulation of many physiological activities. Autophagy is the metabolic process that transports substances in the cytoplasm to the lysosomes for degradation, and involved in the process of many diseases, including cancer. Studies have shown that autophagy activity has a circadian rhythm feature. As the core gene of the circadian rhythm system, clock has participated in the occurrence and development of cancer. The expression of clock whether regulates tumor development by autophagy has not been illustrated at present. In this study, we established a stable clock-knockdown strain of mouse breast cancer cell 4T1 to explore the changes in autophagy activity. The results showed that autophagy-related proteins ATG9A, ATG7, LC3B and Beclin1 (ATG6) were down-regulated with clock-knockdown, and the p62, the key factors of autophagy, was up-regulated. Moreover, clock-knockdown caused significant up-regulation of p65, and inhibition of IκBα and p-AKT，which were the core factors of several signaling pathways involved in autophagy. Serum rhythm-inducing experiments behaved that the expression of LC3B and Beclin1 had rhythmic characteristics，differed from LC3A. The regulative gene clock was initially established to regulate the autophagy-related genes, and the suggested direction of its regulatory pathways.

KEYWORDS:

• Circadian rhythm
• clock gene
• autophagy

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [grant number 31500935] and the Applied Basic Research of Sichuan Province [grant number 2017NFP0073].