UHRF1 Promotes Cell Growth and Metastasis Through Repression of p16ink4a in Colorectal Cancer
UHRF1 Promotes Cell Growth and Metastasis Through Repression of p16ink4a in Colorectal Cancer
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DOI：
10.1245/s10434-011-2194-1
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发表时间：
2012-08-01
影响因子：
3.7
通讯作者：
Qin, Huan-Long
中科院分区：
文献类型：
--
作者：
Wang, Feng;Yang, Yong-Zhi;Qin, Huan-Long
目的 探讨泛素样植物同源结构域和环指结构域 1 (UHRF1) 在结直肠癌 (CRC) 中的表达是否上调、UHRF1 是否促进 CRC 细胞生长和迁移及其分子机制。采用组织免疫组化法检测 144 对原发性 CRC 及其相应癌旁非肿瘤组织中 UHRF1 蛋白的表达情况 微阵列。通过定量逆转录酶-聚合酶链式反应评估了 20 对上述组织和四种结肠癌细胞系中 UHRF1 mRNA 的表达。确定了 UHRF1 表达与人口统计学和临床病理特征的关联。此外，我们还研究了慢病毒介导的UHRF1的RNA干扰（RNAi）对CRC细胞系中细胞增殖和迁移、细胞周期和凋亡以及p16（ink4a）和p21（waf1/cip1）表达的影响。UHRF1在CRC组织和细胞系中过表达。 UHRF1 蛋白表达水平与淋巴结的存在 (P = 0.005)、远端转移 (P = 0.030)、较差的 Dukes 分期 (P = 0.001) 和 p16(ink4a) 表达的缺失 (P = 0.002) 相关。 UHRF1 的 RNAi 抑制增殖和迁移，并诱导细胞凋亡和细胞周期停滞在 G0/G1 期。此外，UHRF1的RNAi增强了CRC细胞中p16(ink4a)的表达，但不增强p21(waf1/cip1)的表达。UHRF1表达在CRC中上调并且与CRC的进展相关。此外，UHRF1 的 RNAi 会降低 CRC 细胞的增殖和迁移，但会增强 CRC 细胞的凋亡，同时增加 p16(ink4a) 的表达。 UHRF1 可能通过抑制 p16(ink4a) 促进 CRC 生长和转移，因此它可以用作 CRC 的生物标志物甚至治疗靶点。
To investigate whether ubiquitin-like with plant homeodomain and ring finger domains 1 (UHRF1) expression is upregulated in colorectal cancer (CRC), whether UHRF1 promotes CRC cell growth and migration and the underlying molecular mechanism.UHRF1 protein expression was determined in 144 pairs of primary CRC and their corresponding adjacent nontumor tissues by immunohistochemistry with tissue microarrays. UHRF1 mRNA expression was assessed in 20 pairs of the above tissues and four colon cancer cell lines by quantitative reverse transcriptase-polymerase chain reaction. Associations of UHRF1 expression with demographic and clinicopathologic features were determined. Additionally, the effects of lentiviral-mediated RNA interference (RNAi) of UHRF1 on cell proliferation and migration, cell cycle and apoptosis, and the expression of p16(ink4a) and p21(waf1/cip1) were investigated in CRC cell lines.UHRF1 was overexpressed in CRC tissues and cell lines. UHRF1 protein expression levels correlated with the presence of lymph nodes (P = 0.005), distal metastasis (P = 0.030), poor Dukes staging (P = 0.001), and absence of p16(ink4a) expression (P = 0.002). RNAi of UHRF1 inhibited proliferation and migration, and induced apoptosis and cell cycle arrest at the G0/G1 phase. Furthermore, RNAi of UHRF1 enhanced the expression of p16(ink4a), but not p21(waf1/cip1), in CRC cells.UHRF1 expression is upregulated in CRC and is associated with the progression of CRC. Moreover, RNAi of UHRF1 decreases proliferation and migration but enhances apoptosis of CRC cells, with increased p16(ink4a) expression. UHRF1 promotes CRC growth and metastasis, likely by repressing p16(ink4a), and thus it may be used as a biomarker or even a therapeutic target for CRC.