ANRIL regulates the proliferation of human colorectal cancer cells in both two- and three-dimensional culture
ANRIL regulates the proliferation of human colorectal cancer cells in both two- and three-dimensional culture
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DOI：
10.1007/s11010-015-2618-5
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发表时间：
2016-01-01
影响因子：
4.3
通讯作者：
Kotake, Yojiro
中科院分区：
文献类型：
--
作者：
Naemura, Madoka;Tsunoda, Toshiyuki;Kotake, Yojiro
ANRIL是由INK4基因座转录而来的非编码RNA，编码p15、p16和ARF三种肿瘤抑制基因。以前的研究表明，ANRIL抑制p15和p16，p15和p16正向调节pRB通路，导致抑制人正常成纤维细胞的细胞衰老。然而，ANRIL在癌细胞增殖中的作用还不是很清楚。在此，我们报道了ANRIL参与了结直肠癌HCT116细胞在二维和三维培养中的增殖。通过转染小干扰RNA和逆转录病毒产生的小发夹RNA来沉默ANRIL，在二维和三维培养中都降低了HCT116细胞的增殖。去除ANRIL的HCT116细胞被停滞在细胞周期的S期。值得注意的是，沉默ANRIL并没有导致INK4基因座表达的激活。这些结果表明，在二维和三维培养中，ANRIL以p15/p16-pRb通路非依赖的方式正向调节HCT116细胞的增殖。
ANRIL is a long noncoding RNA transcribed from the INK4 locus that encodes three tumor suppressor genes, p15, p16, and ARF. Previous studies demonstrated that ANRIL represses p15 and p16, which positively regulate the pRB pathway, leading to repression of cellular senescence of human normal fibroblasts. However, the role of ANRIL in cancer cell proliferation is less well understood. Here we report that ANRIL is involved in the proliferation of colorectal cancer HCT116 cells in two-and three-dimensional culture. Silencing ANRIL by both transfection with small interfering RNA and retrovirally produced small hairpin RNA reduced HCT116 cell proliferation in both two-and three-dimensional culture. HCT116 cells depleted for ANRIL were arrested in the S phase of cell cycle. Notably, silencing ANRIL did not result in the activation of expression of the INK4 locus. These results suggest that ANRIL positively regulates the proliferation of HCT116 cells in two-and three-dimensional culture in a p15/p16-pRB pathway-independent manner.