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MiR-374a/b-5p Suppresses Cell Growth in Papillary Thyroid Carcinoma Through Blocking Exosomal ANXA1-Induced Macrophage M2 Polarization

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Abstract

Papillary thyroid carcinoma (PTC), comprising 85% of all thyroid cancers, is an epithelial malignancy. The potential for malignant transformation in normal cells by thyroid cancer cells via exosomal Annexin A1 (ANXA1) delivery is investigated in this study. Our aim is to determine the impact of PTC cells on macrophage polarization through exosomal ANXA1 secretion and its implications for tumor progression. Exosomes in PTC cells were examined using transmission electron microscopy, exosome labeling, and nanoparticle tracking analysis. Real-time quantitative polymerase chain reaction was employed to quantify gene expression levels. Protein levels were determined through Western blot analysis. The interplay between genes was assessed using luciferase reporter and RNA pull-down assays. Functional experiments were conducted to investigate PTC cell proliferation and apoptosis. Our findings reveal that ANXA1 promotes PTC cell proliferation and inhibits apoptosis. Exosomes derived from PTC cells were found to promote macrophage M2 polarization. ANXA1 stimulates M2 polarization through the activation of the PI3K/AKT pathway. MicroRNA-374a-5p (miR-374a-5p) and microRNA-374b-5p (miR-374b-5p) were identified as inhibitors of ANXA1 expression and PI3K/AKT pathway activity, thereby inhibiting macrophage M2 polarization. Furthermore, miR-374a-5p and miR-374b-5p were observed to suppress PTC cell proliferation through their regulatory action on ANXA1. Our study suggests that miR-374a/b-5p inhibits PTC cell growth by blocking the macrophage M2 polarization induced by exosomal ANXA1.

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  1. The Second Affiliated Hospital of Wannan Medical College, No.10 Kangfu Road, Wuhu, 241001, Anhui, China

    Sanbao Liu

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All results of this study were done by author SL.

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10528_2024_10747_MOESM1_ESM.tif

Supplementary file1 (TIF 2372 kb)—Figure S1. ANXA1 overexpression promotes PTC cell proliferation and suppresses cell apoptosis. A. ANXA1 expression in PTC tissues was analyzed using GEPIA. B. ANXA1 expression in Nthy-ori 3-1 cells and PTC cells was assessed by RT-qPCR. C. The knockdown efficiency of sh-ANXA1-1/2 was validated in TPC-1 and SNU790 cells. D-F. Proliferation assays were conducted to examine the proliferation of TPC-1 and SNU790 cells transfected with sh-ANXA1-1/2. G-H. TUNEL and flow cytometry analysis were performed to investigate TPC-1 and SNU790 cell apoptosis following transfection with sh-ANXA1-1/2. **P<0.01.

10528_2024_10747_MOESM2_ESM.tif

Supplementary file2 (TIF 3803 kb)—Figure S2. Exosomes derived from TPC cells promote proliferation and inhibit apoptosis in Nthy-ori 3-1 cells. A. CCK-8 assay was performed to evaluate the proliferation capacity of Nthy-ori 3-1 cells treated with PTC cell-derived exosomes. B. EdU assay was conducted to assess the proliferation capacity of Nthy-ori 3-1 cells treated with PTC cell-derived exosomes. C. TUNEL assay was utilized to measure the apoptosis levels of Nthy-ori 3-1 cells treated with PTC cell-derived exosomes. **P<0.01.

Supplementary file3 (TIF 2102 kb)—Figure S3. Quantitative analysis of Western blot data.

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Liu, S. MiR-374a/b-5p Suppresses Cell Growth in Papillary Thyroid Carcinoma Through Blocking Exosomal ANXA1-Induced Macrophage M2 Polarization. Biochem Genet (2024). https://doi.org/10.1007/s10528-024-10747-z

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