Silencing lncRNA ZFAS1 or elevated microRNA-135a represses proliferation, migration, invasion and resistance to apoptosis of osteosarcoma cells

Zilong Zhao,Xiafei Lin,Wenxia Li,Yunhui Tong

doi:10.1186/s12935-019-1049-x

Zilong Zhao, Xiafei Lin + Show 2 more

Open Access

https://doi.org/10.1186/s12935-019-1049-x

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Abstract

BackgroundOsteosarcoma (OS) is still a disease with high mortality from malignant tumors in children and adolescents. Due to its poor treatment, this study explored the involvement of lncRNA ZFAS1/microRNA-135a (miR-135a)/apurinic/apyrimidinic exonuclease 1 (APEX1) axis in the regulation of OS growth and metastasis.MethodsZFAS1, miR-135a and APEX1 expression in OS tissues and cells were tested by RT-qPCR and western blot analysis. MG63 cells were transfected with sh-ZFAS1, miR-135a mimic or their controls to unearth theirs functions in the proliferation, colony formation, migration, invasion, cycle entry and apoptosis of MG63 cells by MTT and EdU, colony formation assays, flow cytometry, and Transwell assay, severally. The proliferation related factor (Ki-67, CyclinD1), apoptosis related factor (Bax, Bcl-2) and migration related factor (MMP2, MMP9) protein levels were tested. Tumor volume and weight were detected by subcutaneous tumor xenograft in nude mice.ResultsOverexpressed ZFAS1 and APEX1, and down-regulated miR-135a existed in OS tissues and cells. Silenced ZFAS1 or elevated miR-135a inhibited colony formation and proliferation, cycle progression, migration and invasion while promoted apoptosis of MG63 cells. Silenced ZFAS1 or elevated miR-135a suppressed tumor volume and weight of OS in vivo. LncRNA ZFAS1 promoted APEX1 expression by competitively binding with miR-135a.ConclusionThis study indicates that silenced ZFAS1 or up-regulated miR-135a restrained migration, proliferation and invasion and promoted apoptosis of OS MG63 cells. This study provides a possible theoretical basis for studying the regulatory mechanism of ZFAS1/miR-135a/APEX1 signaling axis on the growth and metastasis of OS.

Highlights

Osteosarcoma (OS) is still a disease with high mortality from malignant tumors in children and adolescents
Overexpressed long noncoding RNA Zinc finger antisense 1 (ZFAS1), apyrimidinic exonuclease 1 (APEX1), and down‐regulated miR‐135a are found in OS tissues The levels of ZFAS1, miR-135a and APEX1 mRNA and the protein level of APEX1 in normal tissue and OS tissue were detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis
The results found that the expression of ZFAS1 with miR-135a has a negative correlation (r = − 0.768, P < 0.05); miR-135a expression was negatively correlated with APEX1 expression (r = − 0.735, P < 0.05) (Fig. 1c, d)

Summary

Introduction

Osteosarcoma (OS) is still a disease with high mortality from malignant tumors in children and adolescents. Due to its poor treatment, this study explored the involvement of lncRNA ZFAS1/microRNA-135a (miR-135a)/ apurinic/apyrimidinic exonuclease 1 (APEX1) axis in the regulation of OS growth and metastasis. Osteosarcoma (OS), a most general cancer, results in plenty of deaths and has various kinds of classifications [1]. The obvious symptom includes onset of pain and swelling in the influenced bone in OS [2]. OS is an infrequent tumor of mesenchymal origin, mostly often influencing adolescents and young adults [3]. At. The long noncoding RNA Zinc finger antisense 1 (lncRNA ZFAS1), a new lncRNA located at 20q13 and is expressed in lots of tissues and organs [5]. ZFAS1 plays an oncogenic part in some kinds of cancers [6].

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