ANRIL regulates the proliferation of human colorectal cancer cells in both two- and three-dimensional culture
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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.
KeywordsLong noncoding RNA ANRIL p15 p16 Colorectal cancer Cell cycle
We thank our laboratory members for their technical assistance and helpful discussions. This work was supported by JSPS KAKENHI Grant Number 26430127 (to YK) and Takeda Science Foundation (to YK).
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Conflict of interest
The authors have no conflict of interest directly relevant to the content of this article.
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