CREPT and p15RS regulate cell proliferation and cycling in chicken DF-1 cells through the Wnt/-catenin pathway
CREPT and p15RS regulate cell proliferation and cycling in chicken DF-1 cells through the Wnt/-catenin pathway
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CREPT 和 p15RS 通过 Wnt/-catenin 通路调节鸡 DF-1 细胞的细胞增殖和循环
DOI：
10.1002/jcb.26277
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发表时间：
2018-01-01
影响因子：
4
通讯作者：
Li, Bichu
中科院分区：
文献类型：
--
作者：
Jin, Kai;Chen, Hao;Li, Bichu
肿瘤细胞周期相关和表达升高蛋白，也称为RPRD1B)和p15RS （p15（INK4b）相关序列，也称为RPRD1A）已被证明在人类中通过Wnt/-catenin通路下游基因调节细胞增殖和改变细胞周期。尽管一些研究已经揭示了悄悄和p15RS调控人类和哺乳动物细胞增殖的机制，但尚不清楚这些基因在家禽中的作用。为了确定悄悄和p15RS在鸡体内的功能，我们检测了悄悄和p15RS在鸡多种组织和DF-1细胞中的表达。然后，我们分别用过表达载体和短发夹RNA （short hairpin RNA, shRNA）载体瞬时转染鸡DF-1细胞，确定过表达或缺失p15RS对细胞增殖的调节作用。结果表明，悄悄地和p15RS表达模式不同，对细胞周期和增殖的影响相反。敲低p15RS表达或过表达p15RS促进细胞增殖，促进细胞周期从G0/G1期向s期和G2/M期转变，而敲低p15RS或过表达p15RS抑制细胞增殖。从机制上讲，Wnt/-catenin通路下游调控基因，包括-catenin、TCF4和Cyclin D1的表达，是通过调控Wnt/-catenin通路下游调控基因的表达来调控DF-1细胞增殖的。由此可见，Wnt/-catenin通路下游调控基因的转录，从而调控鸡DF-1细胞的增殖和细胞周期转变。
The CREPT (cell cycle-related and expression elevated protein in tumor, also known as RPRD1B) and p15RS (p15(INK4b)-related sequence, also known as RPRD1A) have been shown to regulate cell proliferation and alter the cell cycle through Wnt/-catenin pathway downstream genes in human. Although several studies have revealed the mechanism by which CREPT and p15RS regulate cell proliferation in human and mammals, it is still unclear how these genes function in poultry. In order to determine the function of CREPT and p15RS in chicken, we examined the expression of CREPT and p15RS in a variety of chicken tissues and DF-1 cells. Then, we determined the effect of overexpression or depletion of CREPT or p15RS, by transiently transfecting chicken DF-1 cells with overexpression and short hairpin RNA (shRNA) vectors respectively, on the regulation of cell proliferation. The results showed that CREPT and p15RS had different expression patterns and opposite effects on the cell cycling and proliferation. Knockdown of p15RS expression or overexpression of CREPT facilitated cell proliferation by promoting the cell-cycle transition from G0/G1 to S-phase and G2/M, whereas knockdown of CREPT or overexpression of p15RS inhibited cell proliferation. Mechanistically, CREPT and p15RS control DF-1 cell proliferation by regulating the expression of Wnt/-catenin pathway downstream regulatory genes, including -catenin, TCF4, and Cyclin D1. In conclusion, CREPT and p15RS regulate cell proliferation and the cell-cycle transition in chicken DF-1 cells by regulating the transcription of Wnt/-catenin pathway downstream regulatory genes.