Effect of Lacking ZKSCAN3 on Autophagy, Lysosomal Biogenesis and Senescence
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Published:2023-04-24
Issue:9
Volume:24
Page:7786
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Li Xiao-Min1, Wen Jun-Hao1, Feng Ze-Sen1, Wu Yun-Shan1, Li Dong-Yi1, Liang Shan1, Wu Dan1, Wu Hong-Luan1, Li Shang-Mei1, Ye Zhen-Nan1, Yang Chen1, Sun Lin1, Tang Ji-Xin1, Liu Hua-Feng1
Affiliation:
1. Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases, Institute of Nephrology, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524000, China
Abstract
Transcription factors can affect autophagy activity by promoting or inhibiting the expression of autophagic and lysosomal genes. As a member of the zinc finger family DNA-binding proteins, ZKSCAN3 has been reported to function as a transcriptional repressor of autophagy, silencing of which can induce autophagy and promote lysosomal biogenesis in cancer cells. However, studies in Zkscan3 knockout mice showed that the deficiency of ZKSCAN3 did not induce autophagy or increase lysosomal biogenesis. In order to further explore the role of ZKSCAN3 in the transcriptional regulation of autophagic genes in human cancer and non-cancer cells, we generated ZKSCAN3 knockout HK-2 (non-cancer) and Hela (cancer) cells via the CRISPR/Cas9 system and analyzed the differences in gene expression between ZKSCAN3 deleted cells and non-deleted cells through fluorescence quantitative PCR, western blot and transcriptome sequencing, with special attention to the differences in expression of autophagic and lysosomal genes. We found that ZKSCAN3 may be a cancer-related gene involved in cancer progression, but not an essential transcriptional repressor of autophagic or lysosomal genes, as the lacking of ZKSCAN3 cannot significantly promote the expression of autophagic and lysosomal genes.
Funder
National Natural Science Foundation of China Natural Science Foundation of Guangdong Province Guangdong Provincial Key Laboratory of Autophagy and Major Chronic Non-Communicable Diseases Discipline Construction Project of Guangdong Medical University
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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