LncRNA XIST from the bone marrow mesenchymal stem cell derived exosome promotes osteosarcoma growth and metastasis through miR-655/ACLY signal

Abstract

Background Long non-coding RNA X-inactive specific transcript (XIST) regulates the progression of a variety of tumors, including osteosarcoma. Bone marrow mesenchymal stem cells (BMSCs) can be recruited into osteosarcoma tissue and affect the progression by secreting exosomes. However, whether BMSCs derived exosomes transmit XIST to regulate the growth and metastasis of osteosarcoma and the related mechanism are still unclear. Method In this study, BMSCs derived exosomes were used to treat human osteosarcoma cells MG63 and 143B, and the level of XIST in BMSCs was intervened by siRNA. CCK-8, EdU, transwell assays were used to analyze the changes of cell proliferation, migration and invasion. Bioinformatics analysis, RNA pulldown and dual-luciferase reporter gene assays validated the targeted relationship of XIST with miR-655 and the interaction between miR-655 and ACLY 3’-UTR. 143B/LUC cell line was used to establish an animal model of in situ osteosarcoma to verify the found effects of XIST on osteosarcoma. Oil Red O staining, Western blot and so on were used to detect the changes of lipid deposition and protein expression. Results It was found that BMSCs derived exosomes promoted the proliferation, migration and invasion of osteosarcoma cells, and the down-regulation of XIST inhibited this effect. miR-655 mediated the role of BMSCs derived exosomal XIST in promoting the progression of osteosarcoma and down-regulation of miR-655 could reverse the effects of inhibiting XIST on the proliferation, migration and invasion of osteosarcoma cells. Meanwhile, animal level results confirmed that BMSCs derived exosomal XIST could promote osteosarcoma growth and lung metastasis by combining with miR-655. In-depth mechanism study showed that BMSCs derived exosomal XIST combined with miR-655 to increase the protein level of ACLY, which led to lipid deposition and activate β-catenin signal to promote the proliferation, migration and invasion of osteosarcoma cells. Conclusion This study showed that BMSCs derived exosomal XIST could enter osteosarcoma cells, bind and down-regulates the level of miR-655, resulting in an increase in the level of ACLY, thus increasing the lipid deposition and the activity of β-catenin signal to promote the growth and metastasis of osteosarcoma.

An optimized method for Oil Red O staining with the salicylic acid ethanol solution

“…For the selection of cell lines, we used three types of cells commonly used in the laboratory as well as primary adipocytes, which were stained after different treatments. To be specific, 143B is a human osteosarcoma cells line, liposarcoma of bone is a malignant tumour with a fatty phenotype, and positive ORO stains can be observed in 143B or other osteosarcoma cells [ 28 , 29 ]. The APRE-19 human retinal epithelial cells [ 30 , 31 ] were induced by sodium oleate for 48 hours to be positively stained with ORO.…”

Exploring the Impact of Exosomal Cargos on Osteosarcoma Progression: Insights into Therapeutic Potential

“…More recently, exosomal lncRNA X inactive specific transcripts (XIST) bone marrow MSCs promotes OS progression and lung metastasis by down-regulating miR-655 while upregulating ACLY. This leads to heightened lipid synthesis and the activation of the β-catenin signaling pathway, ultimately nurturing malignant OS phenotypes [ 79 ]. Moreover, Li et al’s study discovered the trafficking of exosomal circRNA within TME, showing that exosomal circ_0000190 can be transported from normal cells to OS cells, leading to the alleviation of the malignant phenotypes of OS through the induction of miR-767-5p, which in turn modulate TET1, effectively hindering the progression of OS [ 82 ].…”

Small extracellular vesicle-mediated metabolic reprogramming: from tumors to pre-metastatic niche formation

“…sEV lncRNA X inactive specific transcripts (XIST) promotes cells proliferation and progression in osteosarcoma tissues through a novel miR-655/ACLY signaling. In regard to the mechanism, XIST was shown to down-regulate the miR-655 expression, bringing about the increased ACLY levels, thereby increasing the lipid deposition in cancer cells [ 34 ]. Acetyl-CoA carboxylase (ACC) and fatty acid synthase (FASN) are major lipogenic enzymes in lipid anabolism that were observed to be enhanced by CD147, a transmembrane glycoprotein enriched in sEVs from patients with hepatocellular carcinoma (HCC) [ 35 , 36 ].…”