Effect of tumor-associated macrophages on lncRNA PURPL/miR-363/PDZD2 axis in osteosarcoma cells

Fan He,Wu Jiang,Guoming Ding,Liulong Zhu,Xiaoliang Fan

doi:10.1038/s41420-021-00700-z

Fan He, Wu Jiang + Show 3 more

Open Access

https://doi.org/10.1038/s41420-021-00700-z

Copy DOI

Abstract

Tumor-associated macrophages (TAMs) are known to participate in osteosarcoma (OS) progression. As demonstrated in our previous research, miR-363 played a tumor inhibitory effect in OS cells via lowering the PDZ domain containing 2 (PDZD2) expression. The regulatory roles of TAMs on miR-363/PDZD2 and the internal mechanism relating to long noncoding RNA p53 upregulated regulator of P53 levels (lncRNA PURPL) are examined in this study. TAM-like macrophages were formed by inducing CD14+ peripheral blood mononuclear cells (PBMCs). The TAMs migration was detected after MG-63 cells transfected with miR-363 mimics or inhibitors. We then analyzed the regulatory activity of PURPL on miR-363 expression. We also tested the influences of PURPL overexpression/knockdown on MG-63 cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), as well as TAMs migration. Silence in PDZD2 expression was used to confirm the effects of PURPL on MG-63 cells. We successfully induced TAM-like macrophages. MG-63 cells transfecting miR-363 mimics suppressed TAMs migration while transfecting a converse effect was seen in miR-363 inhibitor. TAMs raised PURPL expression in MG-63 cells, which was an upstream regulator of miR-363. Along with TAMs migration, PURPL overexpression promoted MG-63 cell proliferation, migration, invasion, and EMT. An opposite influence was seen due to the PURPL knockdown. The silence of PDZD2 weakened the influences of PURPL overexpression on MG-63 cells and TAMs migration. On modulating the PURPL/miR-363/PDZD2 axis, TAMs-promoted OS development might be achieved.

Highlights

Osteosarcoma (OS) is a primary malignant bone sarcoma that constantly occurs in the long bones of children and adolescents [1]
MG-63 cells with different miR-363 expressions influenced tumor-associated macrophages (TAMs) migration MG-63 cells were subjected to miR-363 mimics or inhibitor transfection to explore the influence of miR-363 abnormal expression on TAMs migration
To detect metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), X-inactive specific transcript (XIST), NORAD, and p53 upregulated regulator of P53 level (PURPL) expression in MG-63 cells, qPCR was applied after TAMs co-culture

Summary

Introduction

Osteosarcoma (OS) is a primary malignant bone sarcoma that constantly occurs in the long bones of children and adolescents [1]. The long-term survival rate in OS patients remains 10–20% due to the complexity of the pathogenesis and the high rate of tumor metastasis [2]. Several research works in recent years have demonstrated some macrophages, named tumor-associated macrophages (TAMs) that existed in the tumor microenvironment and contributed to the proliferation and metastasis of tumor [4, 5]. Cersosimo et al [6] reported that tumor metastasis and unsatisfied prognosis of OS patients were related to the increased infiltration of M2-like TAMs infiltration. Han et al [7] indicated that via modulating the cyclooxygenase-2 (COX-2)/signal transducer and activator of transcription 3 (STAT3) signaling, TAMs facilitated the epithelial-mesenchymal transition (EMT) and lung metastasis of OS. More investigations are demanded to further find the internal regulatory mechanism of TAMs on OS growth and metastasis

Methods

Results

Conclusion