Enhanced NOLC1 promotes cell senescence and represses hepatocellular carcinoma cell proliferation by disturbing the organization of nucleolus.

Fuwen Yuan,Guodong Li,Tanjun Tong,Yu Zhang,Liwei Ma,Qian Cheng

doi:10.1111/acel.12602

Fuwen Yuan, Guodong Li + Show 4 more

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https://doi.org/10.1111/acel.12602

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Journal: Aging cell	Publication Date: May 10, 2017
Citations: 43	License type: CC BY 4.0

Affiliation: Peking University

Abstract

SummaryThe 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 NOLC1 by stabilizing the 5′UTR of NOLC1 mRNA, and elevated NOLC1 induced the retention of NOG1 in the nucleolus, which is responsible for rRNA processing. Besides, the expression of NOLC1 was negatively correlated with CSIG in the aged mouse tissue and replicative senescent 2BS cells, and the down‐regulation of NOLC1 could rescue CSIG knockdown‐induced 2BS senescence. Additionally, NOLC1 expression was decreased in human hepatocellular carcinoma (HCC) tissue, and the ectopic expression of NOLC1 repressed the proliferation of HCC cells and tumor growth in a HCC xenograft model.

Highlights

The nucleolus is a key organelle that coordinates the synthesis of rRNA and the assembly of ribosomal subunits (Andersen et al, 2005), which play an important role in protein metabolism (Boisvert et al, 2007)
Volcano plot analyses revealed changes in the expression of many genes, and the NOCL1 gene aroused our attention because of its interesting role in the synthesis of rRNA (Fig. 1A). quantitative reverse transcription polymerase chain reaction (qRT–PCR) and Western blot analyses demonstrated that cellular senescence-inhibited gene (CSIG) knockdown increased the expression of NOLC1 (Fig. 1B and C), as well as in human osteosarcoma U2OS and diploid fibroblast 2BS cells (Fig. 1D)
Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd

Summary

Introduction

The nucleolus is a key organelle that coordinates the synthesis of rRNA and the assembly of ribosomal subunits (Andersen et al, 2005), which play an important role in protein metabolism (Boisvert et al, 2007). NOLC1 was first identified as a nuclear localization signal-binding protein that functions as a chaperone for shuttling between the nucleolus and cytoplasm (Meier & Blobel, 1990; Meier & Blobel, 1992). NOLC1 can bind to and inhibit the catalytic subunit of CK2 in vitro (Li et al, 1997; Lee et al, 2013). NOLC1 localizes to nucleolar DFCs and participates in the regulation of rRNA transcription by interacting with the largest subunit of RNA Pol I (RPA194) (Chen et al, 1999; Tsai et al, 2008). Over a decade ago, a report indicated that the ring structures were induced in nucleoli by the exogenous expression of NOLC1 (Isaac et al, 1998, 2001); the underlying mechanisms and biological role remain largely unknown

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