Home HOME Neoplasma Ahead of print Neoplasma Vol.69, No.5, p.1041–1053, 2022

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ISSN 0028-2685
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Neoplasma Vol.69, No.5, p.1041–1053, 2022

Title: Exosomes from M2 macrophages promoted glycolysis in FaDu cells by inhibiting PDLIM2 expression to stabilize PFKL
Author: Peng Wang, Guang-Yao Li, Lei Zhou, Huai-Li Jiang, Yue Yang, Hai-Tao Wu

Abstract: Laryngeal squamous cell carcinoma (LSCC) is one of the most prevalent malignant diseases worldwide. LSCC patients suffer from a severe decline in life quality, due to the essential roles of the larynx in basic functions in a human body. The overarching goal of the present study is to explore whether exosome from M2 macrophages promotes LSCC by targeting glycolysis. In the current study, the expression of PDLIM2, an E3 ubiquitin ligase, in clinical samples was monitored by quantitative PCR and immunohistochemical examination. Extracellular acidification rate (ECAR) and oxygen consumption rate (OCR) were measured by the Seahorse machine. Cell proliferation was measured by using Cell Counting Kit-8. A luciferase assay was performed to verify the regulation of miRNA on its target gene. The results showed that PDLIM2 exhibited downregulation in LSCC clinical samples and was associated with stage and differentiation of tumors in patients. In FaDu cell line, PDLIM2 inhibited cell proliferation and glycolysis but promoted the ubiquitination of PFKL. Exosomes from M2-type macrophages delivered miR-222-3p into LSCC cells to suppress PDLIM2 expression, leading to the elevated expression of PFKL and enhanced glycolysis which accelerated the proliferation of FaDu cells. The findings from cultured cells were supported by a subcutaneous tumor growth model in nude mice. Collectively, our data provided a snapshot of the miR-222-3p/PDLIM2/PFKL axis in LSCC tumorigenesis, and in concert with the importance of TAM exosomes and glycolysis, could be potentially translated to LSCC clinics.

Keywords: aerobic glycolysis; exosome; laryngeal squamous cell carcinoma; tumor-associated macrophage
Published online: 20-Jun-2022
Year: 2022, Volume: 69, Issue: 5 Page From: 1041, Page To: 1053
doi:10.4149/neo_2022_220426N455


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