Exosomal LINC00958 maintains ovarian cancer cell stemness and induces M2 macrophage polarization via Hedgehog signaling pathway and GLI1 protein

• Published in: International journal of biological macromolecules Vol. 279; no. Pt 1; p. 135080
• Main Authors: Yan, Xichan, Yang, Yinong, Guan, Haichen, Zhang, Xuemei, Li, Li, Yu, Penghui
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.11.2024
• Subjects: Exosomal LINC00958; Hedgehog pathway; M2 polarization; Ovarian cancer; Stemness; Exosomal LINC00958; Stemness; M2 polarization; Ovarian cancer; Hedgehog pathway
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.135080

Long non-coding RNA (lncRNA) LINC00958 has been reported to promote many gynecological cancers, but its detailed function in OC remains unclear. Cancer stem cells (CSCs) and tumor-associated macrophages (TAMs) have been reported to participate in the occurrence and metastasis of cancers. We want to explore the effects of exosomal LINC00958 on cell stemness and macrophage polarization in OC. LINC00958 expression was first verified in OC cells and its function on cell stemness was verified by subcellular fractionation analysis, sphere formation assay and so on. Exosomal LINC00958 was secreted from OC cells and the model of M2 macrophage polarization was established to further verify the impact of exosomal LINC00958 on the cell stemness and macrophage polarization of OC cells using several mechanism experiments including flow cytometry, RNA pulldown, luciferase reporter assays and so on. LINC00958 was up-regulated in OC cells and exosomal LINC00958 enhanced the stem cell-like properties of OC cells and M2 macrophage polarization. Furthermore, LINC00958 combined with glioma-associated oncogene homolog 1 (GLI1) to activate Hedgehog pathway, thereby promoting M2 polarization. Exosomal LINC00958 maintained OC cell stemness and induced M2 polarization via the Hedgehog signaling pathway.