Long Noncoding RNA MALAT1 Interacts with miR-124-3p to Modulate Osteosarcoma Progression by Targeting SphK1.

Bin Liu,Xinli Zhan,Chong Liu,Zhiqian Zhang

doi:10.1155/2021/8390165

Abstract

Introduction Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological functions, including tumor proliferation, apoptosis, progression, and metastasis. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in various cancers, as well as osteosarcoma (OS); however, its underlying mechanism in OS is poorly understood. This investigation aims to elucidate the mechanisms of MALAT1 in OS proliferation and migration and to provide theoretical grounding for further targeted therapy in OS. Methods In the present study, we applied qRT-PCR to assess the MALAT1 expression in OS tissues and cell lines. The effects of MALAT1 and miR-124-3p on OS cell proliferation and migration were studied by CCK-8 and scratch assays. Cell cycle and apoptosis were tested using a flow cytometer. The competing relationship between MALAT1 and miR-124-3p was confirmed by dual-luciferase reporter assay. Results MALAT1 was overexpressed in OS cell lines and tissue specimens, and knockdown of MALAT1 significantly inhibited cell proliferation and migration and increased cell apoptosis and the percentage of G0/G1 phase. Furthermore, MALAT1 could directly bind to miR-124-3p and inhibit miR-124-3p expression. Moreover, MALAT1 overexpression significantly relieved the inhibition on OS cell proliferation mediated by miR-124-3p overexpression, which involved the derepression of sphingosine kinase 1 (SphK1). Conclusions We propose that lncRNA MALAT1 interacts with miR-124-3p to modulate OS progression by targeting SphK1. Hence, we identified a novel MALAT1/miR-124-3p/SphK1 signaling pathway in the regulation of OS biological behaviors.

Highlights

Long noncoding RNAs have been implicated in a variety of biological functions, including tumor proliferation, apoptosis, progression, and metastasis. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in various cancers, as well as osteosarcoma (OS); its underlying mechanism in OS is poorly understood.is investigation aims to elucidate the mechanisms of MALAT1 in OS proliferation and migration and to provide theoretical grounding for further targeted therapy in OS
LncRNA MALAT1 Plays an Important Role in Progression of OS. e effect of lncRNA MALAT1 on OS development and progression was investigated. e Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) results showed that MALAT1 was elevated in human OS specimens compared to adjacent healthy tissues (p < 0.01) (Figure 1(a))
We found a negative linear relationship between the expression of miR-124-3p and MALAT1 in OS tissue (Figure 3(a)). e qRT-PCR assay showed that miR-124-3p expression was increased in the si-MALAT1 group when compared with the si-NC group (Figure 3(b)), while MALAT1 expression was decreased in the miR-124-3p overexpression group when compared with the negative control (NC) group (Figure 3(c))

Summary

Introduction

Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological functions, including tumor proliferation, apoptosis, progression, and metastasis. lncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in various cancers, as well as osteosarcoma (OS); its underlying mechanism in OS is poorly understood.is investigation aims to elucidate the mechanisms of MALAT1 in OS proliferation and migration and to provide theoretical grounding for further targeted therapy in OS. Long noncoding RNAs (lncRNAs) have been implicated in a variety of biological functions, including tumor proliferation, apoptosis, progression, and metastasis. LncRNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is overexpressed in various cancers, as well as osteosarcoma (OS); its underlying mechanism in OS is poorly understood. E effects of MALAT1 and miR-124-3p on OS cell proliferation and migration were studied by CCK-8 and scratch assays. MALAT1 was overexpressed in OS cell lines and tissue specimens, and knockdown of MALAT1 significantly inhibited cell proliferation and migration and increased cell apoptosis and the percentage of G0/G1 phase. MALAT1 overexpression significantly relieved the inhibition on OS cell proliferation mediated by miR-124-3p overexpression, which involved the derepression of sphingosine kinase 1 (SphK1). We propose that lncRNA MALAT1 interacts with miR-124-3p to modulate OS progression by targeting SphK1. Recent breakthroughs in the use of targeted therapies in the management of malignant tumors, such as leukemia and lung cancer, bring beneficial inspiration for OS treatment. us, it is essential to explore the molecular mechanisms underlying OS tumorigenesis and progression and to identify clinically relevant biomarkers and targets for OS.

Methods

Results

Discussion

Conclusion