Epithelial cell transforming sequence 2 (ECT2) is expressed at high levels in various malignancies and contributes to malignant phenotypes in cancers. However, ECT2 is still not fully understood regarding its function and carcinogenic mechanism in cervical cancer. This research indicated that ECT2 expression was elevated in cervical cancer based on bioinformatics analysis and clinical specimens. Experiments in vitro and in vivo confirmed that ECT2 knockdown could suppress the proliferation and metastasis of cervical carcinoma cells. In addition, we found that silencing ECT2 could enhance the sensitivity to cisplatin and promote cell apoptosis. Mechanistically, we observed that ECT2 knockdown could inhibit the AKT/mTOR pathway and activate apoptosis, while ECT2 overexpression induced the opposite effect. The relationship between ECT2 and AKT was further confirmed by immunoprecipitation and rescue experiments. We found that the ECT2 and AKT could interact to form a complex, and knockdown AKT could offset all of the effects induced by ECT2. Our study emphasized the key point of ECT2 in the reversal of cisplatin resistance, and ECT2 could become a potential therapeutic target in cervical cancer.
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The datasets generated during and/or analyzed during the current study are available. The RNA-sequencing data has been uploaded in Sequence Read Archive (SRA) (https://www.ncbi.nlm.nih.gov/sra/?term=PRJNA814339).
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We would like to acknowledge all participants in this study.
This research was carried out at Qilu hospital of Shangdong University and supported by the Shandong Province Key Research Project (2017CXGC1210), Natural Science Foundation Youth Project of Shandong Province (ZR2021QH044), Youth Innovation Technology Project of Higher School of Jinan (2021 GXRC027), National Natural Science Foundation of China (81902644), Natural Science Foundation of Shandong Province (ZR2019BC059 and ZR2020QH248), and Science and Technology Development Project of Shandong Province (2019GSF108126).
The authors declare no competing interests.
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Ethics approval of this research was granted by the Ethics Committee of Qilu Hospital of Shandong University. The animal study was reviewed and approved by Institute of Zoology, Shandong University.
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Liu, X., Zhang, J., Ju, S. et al. ECT2 promotes malignant phenotypes through the activation of the AKT/mTOR pathway and cisplatin resistance in cervical cancer. Cancer Gene Ther 30, 62–73 (2023). https://doi.org/10.1038/s41417-022-00525-7