RRC ID 65999
Author Wu DC, Wang SSW, Liu CJ, Wuputra K, Kato K, Lee YL, Lin YC, Tsai MH, Ku CC, Lin WH, Wang SW, Kishikawa S, Noguchi M, Wu CC, Chen YT, Chai CY, Lin CS, Kuo KK, Yang YH, Miyoshi H, Nakamura Y, Saito S, Nagata K, Lin CS, Yokoyama KK.
Title Reprogramming Antagonizes the Oncogenicity of HOXA13-Long Noncoding RNA HOTTIP Axis in Gastric Cancer Cells.
Journal Stem Cells
Abstract Reprogramming of cancer cells into induced pluripotent stem cells (iPSCs) is a compelling idea for inhibiting oncogenesis, especially through modulation of homeobox proteins in this reprogramming process. We examined the role of various long noncoding RNAs (lncRNAs)-homeobox protein HOXA13 axis on the switching of the oncogenic function of bone morphogenetic protein 7 (BMP7), which is significantly lost in the gastric cancer cell derived iPS-like cells (iPSLCs). BMP7 promoter activation occurred through the corecruitment of HOXA13, mixed-lineage leukemia 1 lysine N-methyltransferase, WD repeat-containing protein 5, and lncRNA HoxA transcript at the distal tip (HOTTIP) to commit the epigenetic changes to the trimethylation of lysine 4 on histone H3 in cancer cells. By contrast, HOXA13 inhibited BMP7 expression in iPSLCs via the corecruitment of HOXA13, enhancer of zeste homolog 2, Jumonji and AT rich interactive domain 2, and lncRNA HoxA transcript antisense RNA (HOTAIR) to various cis-element of the BMP7 promoter. Knockdown experiments demonstrated that HOTTIP contributed positively, but HOTAIR regulated negatively to HOXA13-mediated BMP7 expression in cancer cells and iPSLCs, respectively. These findings indicate that the recruitment of HOXA13-HOTTIP and HOXA13-HOTAIR to different sites in the BMP7 promoter is crucial for the oncogenic fate of human gastric cells. Reprogramming with octamer-binding protein 4 and Jun dimerization protein 2 can inhibit tumorigenesis by switching off BMP7. Stem Cells 2017;35:2115-2128.
Volume 35(10)
Pages 2115-2128
Published 2017-10-1
DOI 10.1002/stem.2674
PMID 28782268
MeSH Bone Morphogenetic Protein 7 / genetics Bone Morphogenetic Protein 7 / metabolism Cell Line, Tumor Cell Proliferation Cellular Reprogramming Techniques / methods* Homeodomain Proteins / genetics* Homeodomain Proteins / metabolism Humans Promoter Regions, Genetic RNA, Long Noncoding / genetics* RNA, Long Noncoding / metabolism Stomach Neoplasms / genetics* Stomach Neoplasms / metabolism Stomach Neoplasms / pathology
IF 6.022
Human and Animal Cells 293T(RCB2202)