Paternally expressed gene 10 (PEG10) has been associated with neuroendocrine muscle-invasive bladder cancer (MIBC), a subtype of the disease with the poorest survival. In this work, we further characterized the expression pattern of PEG10 in The Cancer Genome Atlas database of 412 patients with MIBC, and found that, compared with other subtypes, PEG10 mRNA level was enhanced in neuroendocrine-like MIBC and highly correlated with other neuroendocrine markers. PEG10 protein level also associated with neuroendocrine markers in a tissue microarray of 82 cases. In bladder cancer cell lines, PEG10 expression was induced in drug-resistant compared with parental cells, and knocking down of PEG10 resensitized cells to chemotherapy. Loss of PEG10 increased protein levels of cell-cycle regulators p21 and p27 and delayed G1–S-phase transition, while overexpression of PEG10 enhanced cancer cell proliferation. PEG10 silencing also lowered levels of SLUG and SNAIL, leading to reduced invasion and migration. In an orthotopic bladder cancer model, systemic treatment with PEG10 antisense oligonucleotide delayed progression of T24 xenografts. In summary, elevated expression of PEG10 in MIBC may contribute to the disease progression by promoting survival, proliferation, and metastasis. Targeting PEG10 is a novel potential therapeutic approach for a subset of bladder cancers.

中文翻译：

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父本表达的基因 10 (PEG10) 促进膀胱癌的生长、侵袭和存活

父系表达的基因 10 (PEG10) 与神经内分泌肌肉浸润性膀胱癌 (MIBC) 相关，这是一种生存率最低的疾病亚型。在这项工作中，我们进一步表征了 412 名 MIBC 患者癌症基因组图谱数据库中 PEG10 的表达模式，发现与其他亚型相比，PEG10 mRNA 水平在神经内分泌样 MIBC 中增强，并与其他神经内分泌标志物高度相关. PEG10 蛋白水平也与 82 例组织微阵列中的神经内分泌标志物相关。在膀胱癌细胞系中，与亲本细胞相比，在耐药细胞中 PEG10 表达被诱导，并且敲除 PEG10 使细胞对化疗重新敏感。PEG10 的缺失增加了细胞周期调节因子 p21 和 p27 的蛋白质水平，并延迟了 G1-S 期转变，而PEG10的过表达增强了癌细胞的增殖。PEG10 沉默还降低了 SLUG 和 SNAIL 的水平，从而减少了侵袭和迁移。在原位膀胱癌模型中，PEG10 反义寡核苷酸的全身治疗延迟了 T24 异种移植物的进展。总之，MIBC 中 PEG10 的高表达可能通过促进存活、增殖和转移来促进疾病进展。靶向 PEG10 是治疗膀胱癌亚组的一种新型潜在治疗方法。MIBC 中 PEG10 的表达升高可能通过促进存活、增殖和转移来促进疾病进展。靶向 PEG10 是治疗膀胱癌亚组的一种新型潜在治疗方法。MIBC 中 PEG10 的表达升高可能通过促进存活、增殖和转移来促进疾病进展。靶向 PEG10 是治疗膀胱癌亚组的一种新型潜在治疗方法。