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MYC-regulated pseudogene HMGA1P6 promotes ovarian cancer malignancy via augmenting the oncogenic HMGA1/2.
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-03-03 , DOI: 10.1038/s41419-020-2356-9 Xiaoxue Tian 1, 2 , Jianping Song 2 , Xiyu Zhang 3 , Mingyao Yan 2 , Shourong Wang 1, 2 , Yuqiong Wang 4 , Limei Xu 2 , Ling Zhao 2 , Jian-Jun Wei 5 , Changshun Shao 6 , Beihua Kong 1 , Zhaojian Liu 2
Cell Death & Disease ( IF 8.1 ) Pub Date : 2020-03-03 , DOI: 10.1038/s41419-020-2356-9 Xiaoxue Tian 1, 2 , Jianping Song 2 , Xiyu Zhang 3 , Mingyao Yan 2 , Shourong Wang 1, 2 , Yuqiong Wang 4 , Limei Xu 2 , Ling Zhao 2 , Jian-Jun Wei 5 , Changshun Shao 6 , Beihua Kong 1 , Zhaojian Liu 2
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Pseudogenes have long been considered as nonfunctional genomic sequences. Recent studies have shown that they can potentially regulate the expression of protein-coding genes and are dysregulated in diseases including cancer. However, the potential roles of pseudogenes in ovarian cancer have not been well studied. Here we characterized the pseudogene expression profile in HGSOC (high-grade serous ovarian carcinoma) by microarray. We identified 577 dysregulated pseudogenes and most of them were up-regulated (538 of 577). HMGA1P6 (High mobility group AT-hook 1 pseudogene 6) was one of the overexpressed pseudogenes and its expression was inversely correlated with patient survival. Mechanistically, HMGA1P6 promoted ovarian cancer cell malignancy by acting as a ceRNA (competitive endogenous RNA) that led to enhanced HMGA1 and HMGA2 expression. Importantly, HMGA1P6 was transcriptionally activated by oncogene MYC in ovarian cancer. Our findings reveal that MYC may contribute to oncogenesis through transcriptional regulation of pseudogene HMGA1P6 in ovarian cancer.
中文翻译：
MYC调控的假基因HMGA1P6通过增加致癌性HMGA1 / 2来促进卵巢癌恶性肿瘤。
伪基因长期以来一直被认为是非功能性基因组序列。最近的研究表明，它们可以潜在地调节蛋白质编码基因的表达，并在包括癌症在内的疾病中失调。然而，假基因在卵巢癌中的潜在作用尚未得到很好的研究。在这里，我们通过微阵列表征了HGSOC（高级浆液性卵巢癌）中的假基因表达谱。我们鉴定了577个假基因失调，其中大多数被上调（577个中的538个）。HMGA1P6（高迁移率AT钩1类假基因6）是过表达的假基因之一，其表达与患者生存率呈负相关。从机理上讲，HMGA1P6通过充当导致增强HMGA1和HMGA2表达增强的ceRNA（竞争性内源RNA）来促进卵巢癌细胞的恶性程度。重要的是，HMGA1P6在卵巢癌中被癌基因MYC转录激活。我们的发现表明MYC可能通过卵巢癌假基因HMGA1P6的转录调控促进肿瘤发生。
更新日期：2020-03-03
中文翻译：
MYC调控的假基因HMGA1P6通过增加致癌性HMGA1 / 2来促进卵巢癌恶性肿瘤。
伪基因长期以来一直被认为是非功能性基因组序列。最近的研究表明，它们可以潜在地调节蛋白质编码基因的表达，并在包括癌症在内的疾病中失调。然而，假基因在卵巢癌中的潜在作用尚未得到很好的研究。在这里，我们通过微阵列表征了HGSOC（高级浆液性卵巢癌）中的假基因表达谱。我们鉴定了577个假基因失调，其中大多数被上调（577个中的538个）。HMGA1P6（高迁移率AT钩1类假基因6）是过表达的假基因之一，其表达与患者生存率呈负相关。从机理上讲，HMGA1P6通过充当导致增强HMGA1和HMGA2表达增强的ceRNA（竞争性内源RNA）来促进卵巢癌细胞的恶性程度。重要的是，HMGA1P6在卵巢癌中被癌基因MYC转录激活。我们的发现表明MYC可能通过卵巢癌假基因HMGA1P6的转录调控促进肿瘤发生。
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