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
Abstract 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...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2023-12-01
|
| Series: | Cancer Cell International |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12935-023-03173-5 |
| _version_ | 1827399364218191872 |
|---|---|
| author | Peng Xu Da-xiong Feng Jun Wang Yao-Dong Wang Gang Xie Bin Zhang Xiao-Han Li Jia-Wei Zeng Jia-Fu Feng |
| author_facet | Peng Xu Da-xiong Feng Jun Wang Yao-Dong Wang Gang Xie Bin Zhang Xiao-Han Li Jia-Wei Zeng Jia-Fu Feng |
| author_sort | Peng Xu |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-08T19:43:53Z |
| format | Article |
| id | doaj.art-d889aba166f84b748f3f05af4a84e81d |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-03-08T19:43:53Z |
| publishDate | 2023-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-d889aba166f84b748f3f05af4a84e81d2023-12-24T12:29:49ZengBMCCancer Cell International1475-28672023-12-0123112010.1186/s12935-023-03173-5LncRNA 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 pathwayPeng Xu0Da-xiong Feng1Jun Wang2Yao-Dong Wang3Gang Xie4Bin Zhang5Xiao-Han Li6Jia-Wei Zeng7Jia-Fu Feng8NHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaDepartment of Spine Surgery, The Affiliated Hospital of Southwest Medical UniversityDepartment of Laboratory Medicine, Sichuan Provincial Maternity and Child Health Care HospitalNHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaNHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaNHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaDepartment of Medical Laboratory, The Affiliated Hospital of Southwest Medical UniversityNHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaNHC Key Laboratory of Nuclear Technology Medical Transformation (MIANYANG CENTRAL HOSPITAL), Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of ChinaAbstract 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.https://doi.org/10.1186/s12935-023-03173-5Renal cell carcinomaN6-methyladenosineLong non-coding RNAAGAP2-AS1IGF2BP3miR-9-5p |
| spellingShingle | Peng Xu Da-xiong Feng Jun Wang Yao-Dong Wang Gang Xie Bin Zhang Xiao-Han Li Jia-Wei Zeng Jia-Fu Feng 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 Cancer Cell International Renal cell carcinoma N6-methyladenosine Long non-coding RNA AGAP2-AS1 IGF2BP3 miR-9-5p |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| topic | Renal cell carcinoma N6-methyladenosine Long non-coding RNA AGAP2-AS1 IGF2BP3 miR-9-5p |
| url | https://doi.org/10.1186/s12935-023-03173-5 |
| work_keys_str_mv | AT pengxu lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway AT daxiongfeng lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway AT junwang lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway AT yaodongwang lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway AT gangxie lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway AT binzhang lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway AT xiaohanli lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway AT jiaweizeng lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway AT jiafufeng lncrnaagap2antisenserna1stabilizedbyinsulinlikegrowthfactor2mrnabindingprotein3promotesmacrophagem2polarizationinclearcellrenalcellcarcinomathroughregulationofthemicrorna95pthbs2pi3kaktpathway |