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.
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ZBTB28通过调节FIP200和Bcl-XL诱导自噬促进宫颈癌细胞凋亡
DOI：
10.1186/s13046-021-01948-0
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发表时间：
2021-04-30
期刊：
影响因子：
--
通讯作者：
Xiang T
中科院分区：
文献类型：
--
作者：
Li L;Gong Y;Xu K;Chen W;Xia J;Cheng Z;Li L;Yu R;Mu J;Le X;Xiang Q;Peng W;Tang J;Xiang T
背景在妇女常见的可预防癌症中，宫颈癌的发病率最高。如果在早期发现，是可以治愈的。然而，可靠的诊断和预后指标，涉及到宫颈癌的生理和病理调节，是不可用的。在这项研究中，这样一个潜在的标志物，ZBTB 28，其潜在的有用性在宫颈癌assessment.MethodsPublic数据库分析，逆转录聚合酶链反应（PCR），甲基化特异性PCR分析ZBTB 28的表达和启动子甲基化。ZBTB 28在宫颈癌细胞中的重要性进行了评估，通过细胞和分子分析在体外和在vivo.ResultsThis研究评估的抗肿瘤作用的转录因子，ZBTB 28，这是经常沉默在宫颈癌由于其启动子的CpG甲基化。我们发现ZBTB 28直接影响宫颈癌细胞的增殖、凋亡、自噬和肿瘤发生。此外，它增加了癌细胞对紫杉醇、顺铂和5-氟尿嘧啶的化学敏感性。异位ZBTB 28表达抑制裸鼠宫颈癌移植瘤的生长。此外，电子显微镜证实ZBTB 28在宫颈癌细胞中诱导自噬体。ZBTB 28通过降解Bcl-XL、减少Bcl-XL-BECN 1复合物以及与自噬相关基因FIP 200相互作用诱导细胞自噬。ZBTB 28诱导的宫颈癌细胞自噬可通过FIP 200的调节介导细胞凋亡。结论ZBTB 28是一种能够诱导宫颈癌细胞自噬相关凋亡的抑癌基因。因此，ZBTB 28可能是治疗子宫颈癌的靶点。此外，ZBTB 28启动子甲基化分析可能为宫颈癌筛查提供一种新的客观策略。
BackgroundAmong 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.MethodsPublic 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.ResultsThis 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 foundZBTB28to 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 ofBcl-XL, reduction of the Bcl-XL-BECN1 complex, and by interaction with the autophagy-related geneFIP200. ZBTB28-induced autophagy of cervical cancer cells was shown to mediate cellular apoptosis through the regulation of FIP200.ConclusionThese 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.
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