Upregulated PPARG2 facilitates interaction with demethylated AKAP12 gene promoter and suppresses proliferation in prostate cancer.
Upregulated PPARG2 facilitates interaction with demethylated AKAP12 gene promoter and suppresses proliferation in prostate cancer.
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上调的 PPARG2 促进与去甲基化 AKAP12 基因启动子的相互作用并抑制前列腺癌的增殖
DOI：
10.1038/s41419-021-03820-7
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发表时间：
2021-05-22
影响因子：
9
通讯作者：
Dong F
中科院分区：
文献类型：
--
作者：
Li F;Lu T;Liu D;Zhang C;Zhang Y;Dong F
前列腺癌（PCA）是最常见的男性泌尿生殖系统肿瘤之一。然而，PCA发生和发展的分子机制尚未完全阐明。本研究旨在探讨核受体过氧化物酶体增殖物激活受体γ 2（PPARG 2）在PCA中的生物学功能及其分子机制。我们的研究结果表明，PPARG 2在PCA中表达下调，PPARG 2过表达抑制PCA细胞的迁移、集落形成、侵袭和诱导细胞周期阻滞。此外，PPARG 2过表达调节Akt信号通路的激活，以及抑制体内肿瘤生长。PPARG 2过表达可诱导miR-200 b-3 p表达增加，并促进其与AKAP 12基因启动子的相互作用，抑制PCA细胞增殖。我们的研究结果为PPARG 2-AKAP 12轴介导的表观遗传调控网络提供了第一个证据。该研究确定了一种涉及表观遗传修饰的分子机制，该机制可能作为抗前列腺癌的抗肿瘤策略。
Prostate cancer (PCA) is one of the most common male genitourinary tumors. However, the molecular mechanisms involved in the occurrence and progression of PCA have not been fully clarified. The present study aimed to investigate the biological function and molecular mechanism of the nuclear receptor peroxisome proliferator-activated receptor gamma 2 (PPARG2) in PCA. Our results revealed that PPARG2 was downregulated in PCA, and overexpression of PPARG2 inhibited cell migration, colony formation, invasion and induced cell cycle arrest of PCA cells in vitro. In addition, PPARG2 overexpression modulated the activation of the Akt signaling pathway, as well as inhibited tumor growth in vivo. Moreover, mechanistic analysis revealed that PPARG2 overexpression induced increased expression level of miR-200b-3p, which targeted 3′ UTR of the downstream targets DNMT3A/3B, and facilitated interaction with demethylated AKAP12 gene promoter and suppressed cell proliferation in PCA. Our findings provided the first evidence for a novel PPARG2-AKAP12 axis mediated epigenetic regulatory network. The study identified a molecular mechanism involving an epigenetic modification that could be possibly targeted as an antitumoral strategy against prostate cancer.
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影响因子：
7.3
作者：
Brunetti, Leonardo;Loiodice, Fulvio;Laghezza, Antonio
通讯作者：
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PPARG 多态性与 2 型糖尿病患者不明原因的轻度视力丧失相关
影响因子：
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作者：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1601571113
发表时间：
2016-07-19
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
15.3
作者：
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