LncRNA AGAP2 antisense RNA 1 stabilized by insulin-like growth factor 2 mRNA binding protein 3 promotes macrophage M2 polarization in clear cell renal cell carcinoma through regulation of the microRNA-9-5p/THBS2/PI3K-Akt pathway
© 2023. The Author(s)..
BACKGROUND: Increasing evidence highlights the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of renal cell carcinoma (RCC). Here, we explored the mechanism of AGAP2-AS1 in the occurrence and development of clear cell RCC (ccRCC) involving IGF2BP3/miR-9-5p/THBS2.
METHODS: The expressions of AGAP2-AS1, IGF2BP3, miR-9-5p, and THBS2 and their relationship were analyzed by bioinformatics. The targeting relationship between AGAP2-AS1 and miR-9-5p and between miR-9-5p and THBS2 was evaluated with their effect on cell biological behaviors and macrophage polarization assayed. Finally, we tested the effect of AGAP2-AS1 on ccRCC tumor formation in xenograft tumors.
RESULTS: IGF2BP3 could stabilize AGAP2-AS1 through m6A modification. AGAP2-AS1 was highly expressed in ccRCC tissues and cells. The lentivirus-mediated intervention of AGAP2-AS1 induced malignant behaviors of ccRCC cells and led to M2 polarization of macrophages. In addition, THBS2 promoted M2 polarization of macrophages by activating the PI3K/AKT signaling pathway. AGAP2-AS1 could directly bind with miR-9-5p and promote the expression of THBS2 downstream of miR-9-5p. These results were further verified by in vivo experiments.
CONCLUSION: AGAP2-AS1 stabilized by IGF2BP3 competitively binds to miR-9-5p to up-regulate THBS2, activating the PI3K/AKT signaling pathway and inducing macrophage M2 polarization, thus facilitating the development of RCC.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Cancer cell international - 23(2023), 1 vom: 18. Dez., Seite 330 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Xu, Peng [VerfasserIn] |
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| Links: |
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| Themen: |
AGAP2-AS1 |
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| Anmerkungen: |
Date Revised 21.12.2023 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.1186/s12935-023-03173-5 |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM366016792 |
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| 100 | 1 | |a Xu, Peng |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a LncRNA AGAP2 antisense RNA 1 stabilized by insulin-like growth factor 2 mRNA binding protein 3 promotes macrophage M2 polarization in clear cell renal cell carcinoma through regulation of the microRNA-9-5p/THBS2/PI3K-Akt pathway |
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| 500 | |a Date Revised 21.12.2023 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a © 2023. The Author(s). | ||
| 520 | |a BACKGROUND: Increasing evidence highlights the potential role of long non-coding RNAs (lncRNAs) in the biological behaviors of renal cell carcinoma (RCC). Here, we explored the mechanism of AGAP2-AS1 in the occurrence and development of clear cell RCC (ccRCC) involving IGF2BP3/miR-9-5p/THBS2 | ||
| 520 | |a METHODS: The expressions of AGAP2-AS1, IGF2BP3, miR-9-5p, and THBS2 and their relationship were analyzed by bioinformatics. The targeting relationship between AGAP2-AS1 and miR-9-5p and between miR-9-5p and THBS2 was evaluated with their effect on cell biological behaviors and macrophage polarization assayed. Finally, we tested the effect of AGAP2-AS1 on ccRCC tumor formation in xenograft tumors | ||
| 520 | |a RESULTS: IGF2BP3 could stabilize AGAP2-AS1 through m6A modification. AGAP2-AS1 was highly expressed in ccRCC tissues and cells. The lentivirus-mediated intervention of AGAP2-AS1 induced malignant behaviors of ccRCC cells and led to M2 polarization of macrophages. In addition, THBS2 promoted M2 polarization of macrophages by activating the PI3K/AKT signaling pathway. AGAP2-AS1 could directly bind with miR-9-5p and promote the expression of THBS2 downstream of miR-9-5p. These results were further verified by in vivo experiments | ||
| 520 | |a CONCLUSION: AGAP2-AS1 stabilized by IGF2BP3 competitively binds to miR-9-5p to up-regulate THBS2, activating the PI3K/AKT signaling pathway and inducing macrophage M2 polarization, thus facilitating the development of RCC | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a AGAP2-AS1 | |
| 650 | 4 | |a IGF2BP3 | |
| 650 | 4 | |a Long non-coding RNA | |
| 650 | 4 | |a M2 polarization | |
| 650 | 4 | |a N6-methyladenosine | |
| 650 | 4 | |a PI3K/AKT | |
| 650 | 4 | |a Renal cell carcinoma | |
| 650 | 4 | |a THBS2 | |
| 650 | 4 | |a miR-9-5p | |
| 700 | 1 | |a Feng, Da-Xiong |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Jun |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Yao-Dong |e verfasserin |4 aut | |
| 700 | 1 | |a Xie, Gang |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Bin |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Xiao-Han |e verfasserin |4 aut | |
| 700 | 1 | |a Zeng, Jia-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Feng, Jia-Fu |e verfasserin |4 aut | |
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