ZBTB28 induce autophagy via regulating FIP200 and Bcl-XL to facilitate apoptosis of cervical cancer

Abstract

\n BackgroundCervical cancer is a type of cancer with the highest morbidity among the common preventable cancers in women. It is curable if detected in early stage. This kind of carcinoma is in need of reliable diagnostic and prognostic markers that involved in the regulation of its physiologic and pathological processes. However, the functions and mechanism of ZBTB28 in cervical cancer remain unclear.MethodsPublic database analysis, reverse-transcription PCR, and methylation-specific PCR were employed to analyze ZBTB28 expression and methylation. Tumor cellular functions were assessed via corresponding cellular and molecular biological approaches in vitro and in vivo.ResultsOur study contributed to the anti-tumor effect of transcription factor ZBTB28 which is often silenced in cervical cancer due to promoter CpG methylation. Via molecular and cellular approaches, we found that ectopic expression of ZBTB28 directly affected the biological function of cervical cancer including cell proliferation, apoptosis, autophagy and tumorigenesis, as well as chemosensitivity to Paclitaxel, Cisplatin and 5-FU. Ectopic ZBTB28 expression inhibited the growth of cervical cancer xenografts in nude mice. Furthermore, the electron microscopic photograph showed that ZBTB28 could induce the autophagosome in cervical cancer cells. ZBTB28 resulted in autophagy through degradation of Bcl-XL and reduction of the Bcl-XL–BECN1 complex, but also interacted with autophagy-related gene FIP200. It is worth noticing that ZBTB28-induced autophagy of cervical cancer to mediate cell apoptosis through the regulation of FIP200.ConclusionOur findings enriched the functional diversity of ZBTB28 as a tumor suppressor gene, also illustrated that ZBTB28 could lead to autophagy-related apoptosis in cervical cancer, implying that ZBTB28 may be a target for the treatment of carcinoma of uterine cervix, and detection of ZBTB28 methylation can offer a new objective strategy for screening of cervical cancer.