Research Paper Volume 12, Issue 10 pp 9604—9620

KMT2A regulates cervical cancer cell growth through targeting VDAC1

Changlin Zhang1, *, , Yijun Hua2, *, , Huijuan Qiu2, *, , Tianze Liu3, *, , Qian Long2, *, , Wei Liao1, , Jiehong Qiu1, , Nang Wang4, , Miao Chen2, , Dingbo Shi2, , Yue Yan2, , Chuanbo Xie2, , Wuguo Deng2, , Tian Li1, , Yizhuo Li2, ,

  • 1 Department of Gynecology, The Seventh Affiliated Hospital of Sun Yat-Sen University, Shenzhen, China
  • 2 Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center of Cancer Medicine, Guangzhou, China
  • 3 The Fifth Affiliated Hospital, Sun Yat-Sen University, Zhuhai, China
  • 4 College of Life Sciences, Jiaying University, Meizhou, Guangdong, China
* Equal contribution

Received: September 13, 2019       Accepted: April 14, 2020       Published: May 21, 2020
How to Cite

Copyright © 2020 Zhang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Cervical cancer is an aggressive cutaneous malignancy, illuminating the molecular mechanisms of tumorigenesis and discovering novel therapeutic targets are urgently needed. KMT2A is a transcriptional co-activator regulating gene expression during early development and hematopoiesis, but the role of KMT2A in cervical cancer remains unknown. Here, we demonstrated that KMT2A regulated cervical cancer growth via targeting VADC1. Knockdown of KMT2A significantly suppressed cell proliferation and migration and induced apoptosis in cervical cancer cells, accompanying with activation of PARP/caspase pathway and inhibition of VADC1. Overexpression of VDAC1 reversed the KMT2A knockdown-mediated regulation of cell proliferation, migration and apoptosis. The in vivo results from a cervical cancer xenograft mouse model also validated that KMT2A knockdown suppressed tumor growth by inhibiting VDAC1, whereas KMT2A overexpression promoted cervical cancer growth. Moreover, analyses of Biewenga cervix database and clinical samples showed that both KMT2A and VDAC1 were upregulated in cervix squamous cell carcinoma compared with cervix uteri tissues, and their expression was negatively correlated with the differentiation grade of cervical cancer. Our results therefore indicated that the KMT2A/VDAC1 signaling axis may be a potential new mechanism of cervical carcinogenesis.


KMT2A: Lysine methyltransferase 2A; VDAC1: voltage dependent anion channel 1; HPV: human papillomavirus; MLL-1: mixed-lineage leukemia; ALL-1: acute lymphoblastic leukemia 1; MPT: mitochondrial permeability transition; CIN: cervical intraepithelial neoplasia.