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ORIGINAL RESEARCH article

Front. Cell Dev. Biol.
Sec. Cancer Cell Biology
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1490231

ZNF32 histidine 179 and 183 single site mutation and double sites mutation promote the formation of nuclear speckles of this protein, but differentially regulate the proliferation of breast cancer cells

Provisionally accepted
Chaosong Zhong Chaosong Zhong 1,2*Dingshuang Chen Dingshuang Chen 1,2*Junqi Wang Junqi Wang 2*Fei Wang Fei Wang 1,2*Ruiwen Li Ruiwen Li 3*Yanyan Li Yanyan Li 1,2*Di Gong Di Gong 4*
  • 1 Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Chengdu, Sichuan Province, China
  • 2 College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu, Sichuan Province, China
  • 3 Reproductive and endocrine laboratory, Chengdu Woman-Child Central Hospital, Chengdu, 610051 People’s Republic of China, Chengdu, Sichuan Province, China
  • 4 School of Basic Medical Science, Chengdu University, Chengdu, China, Chengdu, Sichuan Province, China

The final, formatted version of the article will be published soon.

    Previous studies found that ZNF32 H 179, 183 A exhibited point-like nuclear speckles, however, the cause of ZNF32 nuclear speckles formation and its effects on breast cancer cells remain unknown. In this study, we constructed ZNF32 H 179, 183 A, H 179 A and H 183 A breast cancer cells, and found ZNF32 nuclear speckles in all three cell types. Transcriptome analysis showed that the appearance of nuclear speckles may be related to the change of the activity of cell growth factor and RNA polymerase II transcription factor. Comprehensive analysis of transcriptomics and metabolomics revealed that the formation of ZNF32 nuclear speckles was accompanied by changes in choline metabolism. Both in vivo and in vitro experiments suggested that ZNF32 H 179 A and H 183 A but not H 179, 183 A could promote breast cancer cell proliferation. We then explored and verified differentially expressed genes by RNA-Seq and qRT-PCR to explain the different proliferation abilities of these mutations. Dual luciferase reporter gene confirmed that ZNF32H 179 A and H 183 A can transcriptionally activate ISY1-RAB43 and UPK3BL1 and inhibit the transcription of SNX22, and this may attribute to the fact that these mutations caused different zinc finger structure changes in ZNF32. This study deepens the understanding of ZNF32 mutation on nuclear speckles formation and their roles in breast cancer cell proliferation.

    Keywords: ZNF32, breast cancer, Nuclear speckles, Mutation, proliferation

    Received: 02 Sep 2024; Accepted: 14 Jan 2025.

    Copyright: © 2025 Zhong, Chen, Wang, Wang, Li, Li and Gong. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Chaosong Zhong, Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Chengdu, Sichuan Province, China
    Dingshuang Chen, Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Chengdu, Sichuan Province, China
    Junqi Wang, College of Animal Husbandry and Veterinary Medicine, Southwest Minzu University, Chengdu, 610041, Sichuan Province, China
    Fei Wang, Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Chengdu, Sichuan Province, China
    Ruiwen Li, Reproductive and endocrine laboratory, Chengdu Woman-Child Central Hospital, Chengdu, 610051 People’s Republic of China, Chengdu, Sichuan Province, China
    Yanyan Li, Qinghai-Tibetan Plateau Animal Genetic Resource Reservation and Utilization Key Laboratory of Sichuan Province, Chengdu, Sichuan Province, China
    Di Gong, School of Basic Medical Science, Chengdu University, Chengdu, China, Chengdu, Sichuan Province, China

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