1. Academic Validation
  2. ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis

ZBTB28 induces autophagy by regulation of FIP200 and Bcl-XL facilitating cervical cancer cell apoptosis

  • J Exp Clin Cancer Res. 2021 Apr 30;40(1):150. doi: 10.1186/s13046-021-01948-0.
Li Li  # 1 2 Yijia Gong  # 1 2 Ke Xu  # 1 2 Weihong Chen 2 Jiuyi Xia 2 Zhaobo Cheng 2 Lili Li 3 Renjie Yu 2 Junhao Mu 2 Xin Le 2 Qin Xiang 2 Weiyan Peng 2 Junying Tang 1 Tingxiu Xiang 4
Affiliations

Affiliations

  • 1 Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 2 Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing, 400016, Yuzhong District, China.
  • 3 Cancer Epigenetics Laboratory, Department of Clinical Oncology, State Key Laboratory of Translational Oncology, Sir YK Pao Center for Cancer and Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
  • 4 Chongqing Key Laboratory of Molecular Oncology and Epigenetics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Chongqing, 400016, Yuzhong District, China. xiangtx@cqmu.edu.cn.
  • # Contributed equally.
Abstract

Background: Among the common preventable cancers of women, cervical Cancer has the highest morbidity. It is curable if detected at an early stage. However, reliable diagnostic and prognostic markers, which relate to physiologic and pathologic regulation of cervical Cancer, are not available. In this study, one such potential marker, ZBTB28, was evaluated for its potential usefulness in cervical Cancer assessment.

Methods: Public database analysis, reverse-transcription polymerase chain reaction (PCR), and methylation-specific PCR were employed to analyze ZBTB28 expression and promoter methylation. The importance of ZBTB28 in cervical Cancer cells was assessed by cellular and molecular analysis in vitro and in vivo.

Results: This study assessed the anti-tumor effects of the transcription factor, ZBTB28, which is often silenced in cervical Cancer due to CpG methylation of its promoter. We found ZBTB28 to directly affect cervical Cancer cell proliferation, Apoptosis, Autophagy, and tumorigenesis. Also, it increased Cancer cell chemosensitivity to Paclitaxel, Cisplatin, and 5-fluorouracil. Ectopic ZBTB28 expression inhibited the growth of cervical Cancer xenografts in nude mice. Furthermore, electron microscopy demonstrated ZBTB28 to induce autophagosomes in cervical Cancer cells. ZBTB28 induced cellular Autophagy by the degradation of Bcl-xL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related gene FIP200. ZBTB28-induced Autophagy of cervical Cancer cells was shown to mediate cellular Apoptosis through the regulation of FIP200.

Conclusion: These findings identify ZBTB28 as a tumor suppressor gene that can induce autophagy-related Apoptosis in cervical Cancer cells. As such, ZBTB28 may be a target for the treatment of uterine-cervical carcinoma. Further, ZBTB28 promoter methylation analysis may offer a new objective strategy for cervical Cancer screening.

Keywords

Apoptosis; Autophagy; BECN1; Cervical cancer; FIP200; ZBTB28.

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