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

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.

LncRNA SCAMP1 disrupts the balance between miR-26a-5p and ZEB2 to promote osteosarcoma cell viability and invasion

“…In addition, lncRNA MALAT1 sponged miR-150-5p and increased the expression of VEGFA and enhanced tumor angiogenesis in osteosarcoma ( 36 ). LncRNA PURPL affected tumor-associated macrophages through modulating miR-363 and PDZD2 in osteosarcoma cells ( 37 ). These studies indicated that lncRNAs critically participate in osteosarcoma progression.…”

Crosstalk among long non-coding RNA, tumor-associated macrophages and small extracellular vesicles in tumorigenesis and dissemination

“…For example, TAMs facilitate OS progression by enhancing the expression of lncRNA p53 upregulated regulator of P53 (PURPL) by influencing the miR-363/PDZ domain containing 2 (PDZD2) axis. PURPL positively regulates TAM migration and promotes OS cell proliferation, migration, invasion, and EMT ( 92 ). This supports the notion that there is feedback regulation and/or crosstalk between lncRNAs and TAMs in tumors.…”

Cryptic binding properties of a transient folding intermediate in a PDZ tandem repeat

“…Despite intense research, 15,[17][18][19][20][21][22][23] understanding the binding of PDZD2 has remained elusive. In fact, notwithstanding its pivotal role in several types of cancers, no clear-cut evidence has been provided to univocally identify a physiological binding partner.…”

“…15,[17][18][19][20][21] Despite its importance, a specific ligand of sPDZD2 has not been directly identified; although previous studies in cellula have suggested an interaction with the C-terminal tail of the D4 immunoglobulin-like domain of the CD4 co-receptor. 22,23 To shed light on the stability and function of sPDZD2, we investigated its pathway of folding and unfolding. As detailed below, we demonstrate the presence of a folding intermediate, which occurs transiently as a consequence of the concurrent denaturation of both PDZ5 and PDZ6.…”

“…Several studies have shown that sPDZD2 is unregulated in several types of cancers 15,17–21 . Despite its importance, a specific ligand of sPDZD2 has not been directly identified; although previous studies in cellula have suggested an interaction with the C‐terminal tail of the D4 immunoglobulin‐like domain of the CD4 co‐receptor 22,23 …”