Open AccessEnhanced NOLC 1 promotes cell senescence and represses hepatocellular carcinoma cell proliferation by disturbing the organization of nucleolus
Author(s) -
Yuan Fuwen,
Zhang Yu,
Ma Liwei,
Cheng Qian,
Li Guodong,
Tong Tanjun
Publication year - 2017
Publication title -
aging cell
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.103
H-Index - 140
eISSN - 1474-9726
pISSN - 1474-9718
DOI - 10.1111/acel.12602
Subject(s) - nucleolus , biology , gene knockdown , ribosome biogenesis , ectopic expression , microbiology and biotechnology , cell growth , senescence , cell , ribosome , gene , rna , cytoplasm , genetics
Summary The nucleolus is a key organelle that is responsible for the synthesis of rRNA and assembly of ribosomal subunits, which is also the center of metabolic control because of the critical role of ribosomes in protein synthesis. Perturbations of rRNA biogenesis are closely related to cell senescence and tumor progression; however, the underlying molecular mechanisms are not well understood. Here, we report that cellular senescence‐inhibited gene ( CSIG ) knockdown up‐regulated NOLC 1 by stabilizing the 5′ UTR of NOLC 1 mRNA , and elevated NOLC 1 induced the retention of NOG 1 in the nucleolus, which is responsible for rRNA processing. Besides, the expression of NOLC 1 was negatively correlated with CSIG in the aged mouse tissue and replicative senescent 2 BS cells, and the down‐regulation of NOLC 1 could rescue CSIG knockdown‐induced 2 BS senescence. Additionally, NOLC 1 expression was decreased in human hepatocellular carcinoma ( HCC ) tissue, and the ectopic expression of NOLC 1 repressed the proliferation of HCC cells and tumor growth in a HCC xenograft model.