LncRNA HCG11 suppresses human osteosarcoma growth through upregulating p27 Kip1.

Jie Gu,Yuanlin Xu,Zhennian He,Junlan Zhu,Xiangqian Meng,Xuchao Shi,Bo Dai

doi:10.18632/aging.203517

Abstract

Osteosarcoma (OS) is a common malignant bone cancer threatening children and young adults. Emerging evidence indicates that long non-coding RNAs (lncRNAs) play crucial roles in the progression of OS. Herein, we want to clarify the roles of lncRNA human leukocyte antigen complex group 11 (HCG11) in OS. Our data revealed that HCG11 expression is decreased in OS, which is a result of transcriptional repression of YY1. Low HCG11 level is closely associated with larger tumor size and shorter overall survival of OS patients. HCG11 negatively regulates cell proliferation, cell cycle, DNA replication in vitro and tumor growth in vivo. HCG11 can raise p27 Kip1 expression via binding to miR-942-5p and IGF2BP2, and p27 Kip1 acts as a key effector for HCG11 exerting biological functions. In conclusion, HCG11 is downregulated in OS, and restrains OS growth both in vitro and in vivo by raising p27 Kip1 expression via binding to miR-942-5p and IGF2BP2.

Highlights

Osteosarcoma (OS) is a common malignant bone cancer that mainly occurs during childhood and adolescence [1, 2]
We found that human leukocyte antigen complex group 11 (HCG11) expression is significantly lower in OS tissues than that in adjacent nontumor tissues (ANTs) (Figure 1A and 1B), and lower in OS cell lines than that in human osteoblast cell line (Figure 1C)
We show that low HCG11 expression is closely associated with www.aging-us.com larger tumor size and shorter overall survival of OS patients, which indicates that HCG11 is a potential biomarker for OS

Summary

Introduction

Osteosarcoma (OS) is a common malignant bone cancer that mainly occurs during childhood and adolescence [1, 2]. OS features a highly malignant phenotype such as uncontrolled growth and invasiveness [3]. Advanced therapies such as surgery combined with multiple chemotherapies have been applied in clinical practice, the outcomes and survival rates of OS patients remain unsatisfactory [4]. Long non-coding RNAs (lncRNAs) are a class of noncoding RNA longer than 200 nucleotides in length [5]. They used to be considered as nonfunctional, while recent studies have shown that lncRNAs play key roles in various aspects of cell biological behavior, including metabolism, proliferation, differentiation, apoptosis and migration [6, 7]. In OS, there have been many studies devoted to investigate the roles of lncRNAs, and identified them as potential markers for diagnostics and therapeutics [10, 11]

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Results

Conclusion