LncRNA-HOXC-AS2 regulates tumor-associated macrophage polarization through the STAT1/SOCS1 and STAT1/CIITA pathways to promote the progression of non-small cell lung cancer
Copyright © 2024 Elsevier Inc. All rights reserved..
Tumor-associated macrophages (TAMs) mainly exhibit the characteristics of M2-type macrophages, and the regulation of TAM polarization is a new target for cancer therapy, among which lncRNAs are key regulatory molecules. This study aimed to explore the effects of lncRNA-HOXC-AS2 on non-small cell lung cancer (NSCLC) by regulating TAM polarization. THP-1 cells were used to differentiate into macrophages, and TAMs were obtained by coculture with A549 cells. The M1/M2 cell phenotype and HOXC-AS2 expression were detected, and A549-derived exosomes (A549-exo) were used to elucidate the effects of A549 on macrophage polarization and HOXC-AS2 expression. Then, by interfering with HOXC-AS2 or STAT1, the effects of HOXC-AS2 regulation of STAT1 on the TAM phenotype and STAT1/SOCS1 and STAT1/CIITA pathways were analyzed, and the proliferation and metastasis of NSCLC cells in the coculture system were also detected. Results showed that HOXC-AS2 expression in M2 macrophages and TAMs was significantly higher than that in M1 macrophages, and A549-exo promoted HOXC-AS2 expression and M2 polarization. Intervention HOXC-AS2 resulted in increased M1 marker expression, decreased M2 marker expression, and activation of STAT1/SOCS1 and STAT1/CIITA pathways in TAMs. In addition, HOXC-AS2 was mainly expressed in the cytoplasm of TAMs and could bind to STAT1. Further experiments confirmed that intervention HOXC-AS2 promoted the M1 polarization of TAMs by targeting STAT1 and weakened the promoting effects of TAMs on the proliferation and metastasis of NSCLC. In conclusion, HOXC-AS2 inhibited the activation of STAT1/SOCS1 and STAT1/CIITA pathways and promoted M2 polarization of TAMs by binding with STAT1, thus promoting NSCLC.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2024 |
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Erschienen: |
2024 |
Enthalten in: |
Zur Gesamtaufnahme - volume:115 |
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Enthalten in: |
Cellular signalling - 115(2024) vom: 22. März, Seite 111031 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Yin, Cunli [VerfasserIn] |
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Links: |
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Anmerkungen: |
Date Completed 22.01.2024 Date Revised 22.03.2024 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.cellsig.2023.111031 |
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funding: |
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Förderinstitution / Projekttitel: |
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PPN (Katalog-ID): |
NLM366592580 |
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245 | 1 | 0 | |a LncRNA-HOXC-AS2 regulates tumor-associated macrophage polarization through the STAT1/SOCS1 and STAT1/CIITA pathways to promote the progression of non-small cell lung cancer |
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520 | |a Copyright © 2024 Elsevier Inc. All rights reserved. | ||
520 | |a Tumor-associated macrophages (TAMs) mainly exhibit the characteristics of M2-type macrophages, and the regulation of TAM polarization is a new target for cancer therapy, among which lncRNAs are key regulatory molecules. This study aimed to explore the effects of lncRNA-HOXC-AS2 on non-small cell lung cancer (NSCLC) by regulating TAM polarization. THP-1 cells were used to differentiate into macrophages, and TAMs were obtained by coculture with A549 cells. The M1/M2 cell phenotype and HOXC-AS2 expression were detected, and A549-derived exosomes (A549-exo) were used to elucidate the effects of A549 on macrophage polarization and HOXC-AS2 expression. Then, by interfering with HOXC-AS2 or STAT1, the effects of HOXC-AS2 regulation of STAT1 on the TAM phenotype and STAT1/SOCS1 and STAT1/CIITA pathways were analyzed, and the proliferation and metastasis of NSCLC cells in the coculture system were also detected. Results showed that HOXC-AS2 expression in M2 macrophages and TAMs was significantly higher than that in M1 macrophages, and A549-exo promoted HOXC-AS2 expression and M2 polarization. Intervention HOXC-AS2 resulted in increased M1 marker expression, decreased M2 marker expression, and activation of STAT1/SOCS1 and STAT1/CIITA pathways in TAMs. In addition, HOXC-AS2 was mainly expressed in the cytoplasm of TAMs and could bind to STAT1. Further experiments confirmed that intervention HOXC-AS2 promoted the M1 polarization of TAMs by targeting STAT1 and weakened the promoting effects of TAMs on the proliferation and metastasis of NSCLC. In conclusion, HOXC-AS2 inhibited the activation of STAT1/SOCS1 and STAT1/CIITA pathways and promoted M2 polarization of TAMs by binding with STAT1, thus promoting NSCLC | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Research Support, Non-U.S. Gov't | |
650 | 4 | |a Non-small cell lung cancer | |
650 | 4 | |a Polarization | |
650 | 4 | |a STAT1/SOCS1 and STAT1/CIITA pathways | |
650 | 4 | |a Tumor-associated macrophage | |
650 | 4 | |a lncRNA-HOXC-AS2 | |
650 | 7 | |a RNA, Long Noncoding |2 NLM | |
650 | 7 | |a SOCS1 protein, human |2 NLM | |
650 | 7 | |a Suppressor of Cytokine Signaling 1 Protein |2 NLM | |
650 | 7 | |a STAT1 protein, human |2 NLM | |
650 | 7 | |a STAT1 Transcription Factor |2 NLM | |
700 | 1 | |a Li, Jing |e verfasserin |4 aut | |
700 | 1 | |a Li, Siru |e verfasserin |4 aut | |
700 | 1 | |a Yang, Xi |e verfasserin |4 aut | |
700 | 1 | |a Lu, Yingchun |e verfasserin |4 aut | |
700 | 1 | |a Wang, Chunyu |e verfasserin |4 aut | |
700 | 1 | |a Liu, Bin |e verfasserin |4 aut | |
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