Down-regulation of miRNA-106b inhibits growth of melanoma cells by promoting G1-phase cell cycle arrest and reactivation of p21/WAF1/Cip1 protein.
Down-regulation of miRNA-106b inhibits growth of melanoma cells by promoting G1-phase cell cycle arrest and reactivation of p21/WAF1/Cip1 protein.
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DOI：
10.18632/oncotarget.2527
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发表时间：
2014-11-15
期刊：
影响因子：
--
通讯作者：
Katiyar SK
中科院分区：
文献类型：
--
作者：
Prasad R;Katiyar SK
miR-106 b在各种类型的癌症中过表达，并与致癌过程的调节有关。使用RT-PCR，我们已经鉴定了miRNA-106 b在各种黑色素瘤细胞系（A375、Hs 294 t、SK-Mel 28、SK-Mel 119、Mel 1241、Mel 1011和Mel 928）中的过表达，与其在正常人表皮黑色素细胞（NHEM）中的表达相比。miR-106 b在黑色素瘤细胞（A375，Hs 294 t）中的过表达与比NHEM更大的细胞增殖能力相关。用抗miR-106 b处理A375和Hs 294 t细胞导致细胞增殖抑制以及G1期停滞。我们确定了葡萄籽原花青素（GSPs）对miRNA-106 b及其潜在分子靶点表达的影响。用GSPs处理A375和Hs 294 t细胞导致miRNA-106 b水平的抑制、细胞毒性、G1期阻滞和p21/WAF 1/Cip 1的重新激活。饮食中的GSP显著抑制裸鼠中A375黑素瘤细胞肿瘤异种移植物的生长，这与miRNA-106 b水平的降低、肿瘤细胞增殖和p21/WAF 1/Cip 1蛋白水平的增加相关。这些研究表明，miRNA-106 b在黑色素瘤生长中起着至关重要的作用，并且GSPs作为miR-106 b的抑制剂，从而在体外和体内模型中阻断黑色素瘤生长。
MiR-106b is overexpressed in various types of cancers and is associated with the regulation of the carcinogenic processes. Using RT-PCR, we have identified overexpression of miRNA-106b in various melanoma cell lines (A375, Hs294t, SK-Mel28, SK-Mel 119, Mel 1241, Mel 1011 and Mel 928) as compared to its expression in normal human epidermal melanocytes (NHEM). The overexpression of miR-106b in melanoma cells (A375, Hs294t) was associated with greater cell proliferation capacity than NHEM. Treatment of A375 and Hs294t cells with anti-miR-106b resulted in inhibition of cell proliferation as well as G1-phase arrest. We determined the effects of grape seed proanthocyanidins (GSPs) on the expression of miRNA-106b and its underlying molecular targets. Treatment of A375 and Hs294t cells with GSPs resulted in suppression of the levels of miRNA-106b, cytotoxicity, G1-phase arrest and reactivation of p21/WAF1/Cip1. Dietary GSPs significantly inhibited growth of A375 melanoma cell tumor xenografts in nude mice, which was associated with reduction in the levels of miRNA-106b, tumor cell proliferation and increases in the levels of p21/WAF1/Cip1 protein. These studies suggest that miRNA-106b plays a crucial role in melanoma growth and that GSPs act as an inhibitor of miR-106b thereby blocking melanoma growth in vitro and in vivo models.
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