Abstract
Cervical cancer (CC) is the second most common type of cancer in women, and presents a serious threat to public health. We aimed to investigate the regulatory impacts of CDGSH iron-sulfur domain-containing protein 2 (CISD2) in CC and to discuss its relationship with E2F transcription factor 7 (E2F7). With the employment of real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blot, the expression of CISD2 and E2F7 in SiHa cells before or after transfection was estimated. Cell counting kit-8 (CCK-8) assay, Terminal deoxynucleotidyl transferase (TdT) dUTP Nick-End Labeling (TUNEL) assay, wound healing and transwell were used to detect the proliferation, apoptosis, migration and invasion of SiHa cells. The activity of CISD2 was detected using luciferase report assay and chromatin immunoprecipitation (ChIP) assay was used to confirm the binding of E2F7 and CISD2 promoter. The contents of proliferation- and apoptosis-related proteins were detected using western blot. Results revealed that CISD2 expression was greatly enhanced in CC cell lines. CISD2 depletion inhibited the proliferation, migration and invasion of SiHa cells but promoted the cell apoptosis. It was also found that E2F7 was remarkably elevated in SiHa cells. According to JASPAR database, the binding sites of E2F7 and CISD2 were predicted and ChIP confirmed the binding of E2F7 and CISD2 promoter. Results obtained from luciferase report assay indicated that E2F7 overexpression increased the activity of CISD2 promoter region. Furthermore, further functional experiments demonstrated that the impacts of E2F7 interference on the proliferation, migration, invasion and apoptosis of SiHa cells were reversed by CISD2 overexpression. In summary, CISD2 silence could alleviate the malignant progression of CC and could be transcribed by E2F7.
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This work was supported by the Natural Science Research Project of Anhui Educational Committee (Project No. KJ2021A0754) and Bengbu Science and Technology Innovation Guidance Project in 2021 (Project No. 20210337).
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Lingling Wang, Yan Wang and Guoliu Ye designed the study and conducted the experiments. Lingling Wang, Caizhi Wang and Kang Yang analyzed the data. Yan Wang and Caizhi Wang drafted the manuscript and interpreted the data. Kang Yang and Guoliu Ye revised the manuscript for important intellectual content. All authors have read and approved the final version of the manuscript.
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Wang, L., Wang, Y., Wang, C. et al. CISD2 transcriptional activated by transcription factor E2F7 promotes the malignant progression of cervical cancer. J Mol Histol 54, 489–498 (2023). https://doi.org/10.1007/s10735-023-10145-6
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DOI: https://doi.org/10.1007/s10735-023-10145-6