RRC ID 52854
Author Kondo A, Nonaka A, Shimamura T, Yamamoto S, Yoshida T, Kodama T, Aburatani H, Osawa T.
Title Long Noncoding RNA JHDM1D-AS1 Promotes Tumor Growth by Regulating Angiogenesis in Response to Nutrient Starvation.
Journal Mol Cell Biol
Abstract Long noncoding RNAs play a pivotal role in tumor progression, but their role in cancer cells in the nutrient-starved tumor microenvironment remains unknown. Here, we show that a nutrient starvation-responsive long noncoding RNA, JHDM1D antisense 1 (JHDM1D-AS1), promotes tumorigenesis by regulating angiogenesis in response to nutrient starvation. Expression of JHDM1D-AS1 was increased in cancer cells. In addition, expression of JHDM1D-AS1 was increased in clinical tumor samples compared to that in normal tissue. Stable expression of JHDM1D-AS1 in human pancreatic cancer (PANC-1 and AsPC-1) cells promoted cell growth in vitro Remarkably, these JHDM1D-AS1-expressing cells showed a significant increase in tumor growth in vivo that was associated with increased formation of CD31+ blood vessels and elevated infiltration of CD11b+ macrophage lineage cells into tumor tissues. Genome-wide analysis of tumor xenografts revealed that expression of genes for tumor-derived angiogenic factors such as hHGF and hFGF1 concomitant with host-derived inflammation-responsive genes such as mMmp3, mMmp9, mS100a8, and mS100a9 was increased in tumor xenografts of JHDM1D-AS1-expressing pancreatic cancer cells, leading to a poor prognosis. Our results provide evidence that increased JHDM1D-AS1 expression under nutrient starvation accelerates tumor growth by upregulating angiogenesis, thus laying the foundation for improved therapeutic strategies.
Volume 37(18)
Published 2017-9-15
DOI 10.1128/MCB.00125-17
PII MCB.00125-17
PMID 28652266
PMC PMC5574049
MeSH Animals Calgranulin A / biosynthesis Calgranulin B / biosynthesis Carcinogenesis / genetics* Cell Line, Tumor Cell Proliferation Fibroblast Growth Factor 1 / biosynthesis Gene Expression Profiling Gene Expression Regulation, Neoplastic / genetics* Hepatocyte Growth Factor / biosynthesis Humans Matrix Metalloproteinase 3 / biosynthesis Matrix Metalloproteinase 9 / biosynthesis Mice Mice, SCID Neoplasm Transplantation Neoplasms / genetics Neoplasms / pathology* Neovascularization, Pathologic / genetics* RNA Interference RNA, Long Noncoding / biosynthesis RNA, Long Noncoding / genetics RNA, Small Interfering / genetics Starvation / genetics* Transplantation, Heterologous Tumor Microenvironment / physiology
IF 3.611
DNA material pMX-puro-hJHDM1D-AS1 (RDB15920).