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Siqi Xu,Xiaoyan Wu,Zhihua Tao,Hongsheng Li1,Chenliang Fan,Songjin Chen,Jianwei Guo,Yao Ning,Xuqi Hu 한국유전학회 2020 Genes & Genomics Vol.42 No.3
Background Androgen-independent prostate cancer (AIPC) is an extremely malignant tumor developed from the androgen dependent (ADPC). However, the mechanism of transition process from ADPC to AIPC remains unknown. Objective Here we aimed to identify the androgen receptor (AR) target gene and its roles in AIPC. Methods Target genes of AR were identified by ChIP-seq in AIPC cells. AR target gene PCDH7 was detected by real time PCR and western blot. Methylation of PCDH7 was measured by bisulfite sequencing and bisulfite amplicon sequencing. Cell growth, invasion and apoptosis were measured by CCK-8, transwell and flow cytometry, respectively. Results AR was significantly enriched in the upstream of PCDH7 gene. The expression of PCDH7 was significantly decreased, while the methylation of PCDH7 was increased in the AIPC cells compared to the ADPC cells. DNA methyltransferase inhibitor significantly suppressed the methylation and increased the mRNA and protein level of PCDH7. Moreover, overexpression of DNMT1 remarkably reduced the mRNA and protein level of PCDH7. DNA methyltransferase inhibitor decreased the cell growth and invasion while promote the cell apoptosis in the AIPC cells. AR significantly target PCDH7, whose hypermethylation may repress cell growth and invasion, and promote apoptosis in AIPC. Conclusions This study might provide a novel potential target for the treatment of AIPC.
Cell-in-Cell Death Is Not Restricted by Caspase-3 Deficiency in MCF-7 Cells
Shan Wang,Meifang He,Linmei Li,Zhihua Liang,Zehong Zou,Ailin Tao 한국유방암학회 2016 Journal of breast cancer Vol.19 No.3
Cell-in-cell structures are created by one living cell entering another homotypic or heterotypic living cell, which usually leads to the death of the internalized cell, specifically through caspase-dependent cell death (emperitosis) or lysosome-dependent cell death (entosis). Although entosis has attracted great attention, its occurrence is controversial, because one cell line used in its study (MCF-7) is deficient in caspase-3. Methods: We investigated this issue using MCF-7 and A431 cell lines, which often display cell-in-cell invasion, and have different levels of caspase-3 expression. Cell-in-cell death morphology, microstructures, and signaling pathways were compared in the two cell lines. Results: Our results confirmed that MCF-7 cells are caspase-3 deficient with a partial deletion in the CASP-3 gene. These cells underwent cell death that lacked typical apoptotic properties after staurosporine treatment, whereas caspase-3-sufficient A431 cells displayed typical apoptosis. The presence of caspase-3 was related neither to the lysosome-dependent nor to the caspase-dependent cell-in-cell death pathway. However, the existence of caspase-3 was associated with a switch from lysosome-dependent cell-in-cell death to the apoptotic cell-in-cell death pathway during entosis. Moreover, cellular hypoxia, mitochondrial swelling, release of cytochrome C, and autophagy were observed in internalized cells during entosis. Conclusion: The occurrence of caspase-independent entosis is not a cell-specific process. In addition, entosis actually represents a cellular self-repair system, functioning through autophagy, to degrade damaged mitochondria resulting from cellular hypoxia in cell-in-cell structures. However, sustained autophagy-associated signal activation, without reduction in cellular hypoxia, eventually leads to lysosome-dependent intracellular cell death.