Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells.
Reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells.
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PCGEM1 和 miR-145 的相互调节促进 LNCaP 前列腺癌细胞的增殖。
DOI：
10.1186/s13046-014-0072-y
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发表时间：
2014-09-10
期刊：
影响因子：
--
通讯作者：
Li YG
中科院分区：
文献类型：
--
作者：
He JH;Zhang JZ;Han ZP;Wang L;Lv YB;Li YG
前列腺癌基因表达标记1(PCGEM1)是一种在前列腺癌(Pca)细胞中过表达的长非编码RNA(LncRNA)，促进前列腺癌的发生和发展，并对化疗诱导的细胞凋亡具有保护作用。MicroRNA miR-145在PCa中作为肿瘤抑制因子发挥作用。我们推测PCGEM1和miR-145的相互调控促进了LNCaP前列腺癌细胞的增殖。为了验证这一假设，我们使用荧光素酶报告实验研究了PCGEM1和miR-145之间的相互作用。通过转染miR-145或针对(SiRNA)PCGEM1的小干扰RNA序列，选择性地改变了LNCaP细胞和非癌RWPE-1前列腺细胞中的表达水平。RT-PCR检测肿瘤细胞相对表达水平，四甲基偶氮唑盐比色法检测肿瘤细胞生长，流式细胞仪检测肿瘤细胞早期凋亡，Transwell法检测肿瘤细胞迁移侵袭特性。在(nu/nu)小鼠模型中检测siRNA、PCGEM1和miR-145对前列腺癌体内生长的影响。PCGEM1和miR-145在LNCaP细胞中的表达呈相互调节，下调PCGEM1的表达可增加miR-145的表达，而过表达miR-145则降低PCGEM1的表达。转染miR-145表达载体和siRNA PCGEM1在体外均能抑制肿瘤细胞的增殖、迁移和侵袭，并诱导早期细胞凋亡。相反，对RWPE-1细胞没有影响。我们证明了PCGEM1和miR-145之间的相互负控制关系，它同时调节LNCaP细胞的增殖和nu/nu PCA肿瘤的生长。研究结果还确定PCGEM1和相关的调节因子可能是PCA治疗的靶点。
Prostate cancer gene expression marker 1 (PCGEM1) is a long non-coding RNA (lncRNA) overexpressed in prostate cancer (PCa) cells that promotes PCa initiation and progression, and protects against chemotherapy-induced apoptosis. The microRNA miR-145 functions as a tumor suppressor in PCa. We speculate that reciprocal regulation of PCGEM1 and miR-145 promote proliferation of LNCaP prostate cancer cells. To test this hypothesis, the interaction between PCGEM1 and miR-145 was examined using a luciferase reporter assay. Expression levels were selectively altered in LNCaP cells and noncancerous RWPE-1 prostate cells by transfection of miR-145 or small interfering RNA sequences against (siRNA) PCGEM1. Relative expression levels were detected by RT-PCR, tumor cell growth and early apoptosis by the MTT assay and flow cytometry, respectively, and tumor cell migration and invasion properties by transwell assays. The effect of siRNA PCGEM1 and miR-145 transfection on prostate cancer growth in vivo was examined in the (nu/nu) mouse model. PCGEM1 and miR-145 exhibited reciprocal regulation; downregulation of PCGEM1 expression in LNCaP cells increased expression of miR-145, while overexpression of miR-145 decreased PCGEM1 expression. Transfection of the miR-145 expression vector and siRNA PCGEM1 inhibited tumor cell proliferation, migration, and invasion, and induced early apoptosis both in vitro. In contrast, there was no effect on RWPE-1 cells. We demonstrate a reciprocal negative control relationship between PCGEM1 and miR-145 that regulates both LNCaP cell proliferation and nu/nu PCa tumor growth. The results also identify PCGEM1 and associated regulators as possible targets for PCa therapy.
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影响因子：
8
作者：
Braconi, C.;Kogure, T.;Valeri, N.;Huang, N.;Nuovo, G.;Costinean, S.;Negrini, M.;Miotto, E.;Croce, C. M.;Patel, T.
通讯作者：
Patel, T.
Diana-LNCBASE：长期非编码RNA上经过实验验证和计算预测的microRNA靶标。
影响因子：
14.9
作者：
Paraskevopoulou MD;Georgakilas G;Kostoulas N;Reczko M;Maragkakis M;Dalamagas TM;Hatzigeorgiou AG
通讯作者：
Hatzigeorgiou AG
影响因子：
37.3
作者：
Augoff K;McCue B;Plow EF;Sossey-Alaoui K
通讯作者：
Sossey-Alaoui K
影响因子：
3.4
作者：
Hajjari, Mohammadreza;Behmanesh, Mehrdad;Zeinoddini, Mehdi
通讯作者：
Zeinoddini, Mehdi
RNA在意外的地方：长的非编码RNA在不同的细胞环境中起作用。
DOI：
10.1038/nrm3679
发表时间：
2013-11
期刊：
Nature reviews. Molecular cell biology
影响因子：
--
作者：
Geisler S;Coller J
通讯作者：
Coller J