Int J Biol Sci 2021; 17(14):3875-3888. doi:10.7150/ijbs.62517 This issue

Research Paper

Up-regulation of MELK by E2F1 promotes the proliferation in cervical cancer cells

Hongzhi Sun1#, Hongmei Ma2#, Hao Zhang3✉, Minjun Ji4,5✉

1. Department of Orthopaedics, Nanjing Jiangbei Hospital affiliated to Nantong University, Nanjing, Jiangsu, 210048, China.
2. Department of Obstetrics and Gynecology, Ma'anshan People's Hospital, Ma'anshan, Anhui, 243000, China.
3. State Key Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
4. Department of Pathogen Biology, Nanjing Medical University, Nanjing, Jiangsu, 211166, China.
5. Jiangsu Province Key Laboratory of Modern Pathogen Biology, Nanjing, Jiangsu, 211166, China.
#These authors contributed equally to this work.

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Citation:
Sun H, Ma H, Zhang H, Ji M. Up-regulation of MELK by E2F1 promotes the proliferation in cervical cancer cells. Int J Biol Sci 2021; 17(14):3875-3888. doi:10.7150/ijbs.62517. Available from https://www.ijbs.com/v17p3875.htm

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Abstract

Graphic abstract

Cervical cancer is a common gynecologic cancer and a frequent cause of death. In this study, we investigated the role of MELK (maternal embryonic leucine zipper kinase) in cervical cancer. We found that HPV 18 E6/E7 promoted MELK expression by activating E2F1. MELK knockdown blocked cancer cells growth. Furthermore, we used MELK-8A to inhibit the kinase activity of MELK and caused the G2/M phase arrest of cancer cells. Under the treatment of inhibitors, Hela cells formed multipolar spindles and eventually underwent apoptosis. We also found that MELK is involved in protein translation and folding during cell division through the MELK interactome and the temporal proteomic analysis under inhibition with MELK-8A. Altogether, these results suggest that MELK may play a vital role in cancer cell proliferation and indicate a potential therapeutic target for cervical cancer.

Keywords: MELK, HPV E6/E7, E2F1, MELK-8A, Cell arrest, Polyploidy