title: ANRIL regulates the proliferation of human colorectal cancer cells in both two- and three-dimensional culture.
abstract: 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.
authors.affiliation: Graduate School of Humanity-Oriented Science and Engineering, Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka, 820-8555, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Naemura
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Tsunoda
authors.affiliation: Graduate School of Humanity-Oriented Science and Engineering, Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka, 820-8555, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Inoue
authors.affiliation: Graduate School of Humanity-Oriented Science and Engineering, Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka, 820-8555, Japan.
authors.forename: Haruna
authors.initials: H
authors.lastname: Okamoto
authors.affiliation: Department of Cell Biology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, 814-0180, Japan.
authors.forename: Senji
authors.initials: S
authors.lastname: Shirasawa
authors.affiliation: Graduate School of Humanity-Oriented Science and Engineering, Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka, 820-8555, Japan. ykotake@fuk.kindai.ac.jp.|Department of Biological and Environmental Chemistry, Faculty of Humanity-Oriented Science and Engineering, Kinki University, 11-6 Kayanomori, Iizuka, Fukuoka, 820-8555, Japan. ykotake@fuk.kindai.ac.jp.
authors.forename: Yojiro
authors.initials: Y
authors.lastname: Kotake
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D015179:Colorectal Neoplasms / Q000473:pathology*; D020868:Gene Silencing; D006801:Humans; D062085:RNA, Long Noncoding / Q000235:genetics / Q000502:physiology*
chemical_list: C561518:CDKN2B antisense RNA, human; D062085:RNA, Long Noncoding
keywords: ANRIL; Cell cycle; Colorectal cancer; Long noncoding RNA; p15; p16