Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression
Background: It has been known for decades that circRNAs are deregulated in cancer. Here, we characterized the role and underlying mechanism of circ_0088212 in osteosarcoma. Methods: The expression levels of circ_0088212, miR-520 h, and APOA1 were determined by RT-qPCR. RNase R digestion was performe...
| Main Authors: | , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-12-01
|
| Series: | Translational Oncology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523321002114 |
| _version_ | 1819021183756009472 |
|---|---|
| author | Feng Liu Xiangyang Zhang Fei Wu Hao Peng |
| author_facet | Feng Liu Xiangyang Zhang Fei Wu Hao Peng |
| author_sort | Feng Liu |
| collection | DOAJ |
| description | Background: It has been known for decades that circRNAs are deregulated in cancer. Here, we characterized the role and underlying mechanism of circ_0088212 in osteosarcoma. Methods: The expression levels of circ_0088212, miR-520 h, and APOA1 were determined by RT-qPCR. RNase R digestion was performed to verify the circular structure of circ_0088212. CCK8 and transwell invasion assays were conducted to examine the in vitro malignancy of osteosarcoma. Caspase-3 activity was also measured.An in vivo model of osteosarcoma was constructed to examine the in vivo effect of circ_0088212 on osteosarcoma. Luciferase reporter, RNA RIP, and RNA pull-down assays were performed to verify the interaction between miR-520 h and APOA1 or circ_0088212. Results: Circ_0088212 and APOA1 were expressed at low levels in osteosarcoma tissues and cells, while miR-520 h was highly expressed. Overexpression of circ_0088212 was found to inhibit the in vitro and in vivo growth of osteosarcoma. Mechanistically, miR-520 h was the target of circ_0088212 and APOA1 was the target of miR-520 h. Circ_0088212 downregulated miR-520 h expression, while miR-520 h overexpression abolished the inhibitory effect of circ_0088212 on osteosarcoma cell proliferation and migration. Furthermore, miR-520 h overexpression led to reduced APOA1 expression, while APOA1 overexpression counteracted the oncogenic effect of miR-520 h in osteosarcoma cells. Conclusion: Our findings demonstrated that circ_0088212 might exert a tumor-suppressive activity in osteosarcoma by sponging and sequestering miR-520 h away from APOA1. This suggests that the circ_0088212/miR-520 h/APOA1 axis may be a promising therapeutic target for osteosarcoma intervention. |
| first_indexed | 2024-12-21T04:03:03Z |
| format | Article |
| id | doaj.art-a6586bc054e44c3ab541a18f42f9be48 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 |
| language | English |
| last_indexed | 2024-12-21T04:03:03Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-a6586bc054e44c3ab541a18f42f9be482022-12-21T19:16:40ZengElsevierTranslational Oncology1936-52332021-12-011412101219Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progressionFeng Liu0Xiangyang Zhang1Fei Wu2Hao Peng3Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, ChinaDepartment of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, ChinaCorresponding author at: Department of Orthopedics, Renmin Hospital of Wuhan University, No. 238, Jiefang Road, Wuchang District, Wuhan 430060, Hubei, China.; Department of Orthopedics, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, ChinaBackground: It has been known for decades that circRNAs are deregulated in cancer. Here, we characterized the role and underlying mechanism of circ_0088212 in osteosarcoma. Methods: The expression levels of circ_0088212, miR-520 h, and APOA1 were determined by RT-qPCR. RNase R digestion was performed to verify the circular structure of circ_0088212. CCK8 and transwell invasion assays were conducted to examine the in vitro malignancy of osteosarcoma. Caspase-3 activity was also measured.An in vivo model of osteosarcoma was constructed to examine the in vivo effect of circ_0088212 on osteosarcoma. Luciferase reporter, RNA RIP, and RNA pull-down assays were performed to verify the interaction between miR-520 h and APOA1 or circ_0088212. Results: Circ_0088212 and APOA1 were expressed at low levels in osteosarcoma tissues and cells, while miR-520 h was highly expressed. Overexpression of circ_0088212 was found to inhibit the in vitro and in vivo growth of osteosarcoma. Mechanistically, miR-520 h was the target of circ_0088212 and APOA1 was the target of miR-520 h. Circ_0088212 downregulated miR-520 h expression, while miR-520 h overexpression abolished the inhibitory effect of circ_0088212 on osteosarcoma cell proliferation and migration. Furthermore, miR-520 h overexpression led to reduced APOA1 expression, while APOA1 overexpression counteracted the oncogenic effect of miR-520 h in osteosarcoma cells. Conclusion: Our findings demonstrated that circ_0088212 might exert a tumor-suppressive activity in osteosarcoma by sponging and sequestering miR-520 h away from APOA1. This suggests that the circ_0088212/miR-520 h/APOA1 axis may be a promising therapeutic target for osteosarcoma intervention.http://www.sciencedirect.com/science/article/pii/S1936523321002114cirRNAmiRNASpongeProliferationOsteosarcoma |
| spellingShingle | Feng Liu Xiangyang Zhang Fei Wu Hao Peng Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression Translational Oncology cirRNA miRNA Sponge Proliferation Osteosarcoma |
| title | Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression |
| title_full | Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression |
| title_fullStr | Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression |
| title_full_unstemmed | Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression |
| title_short | Hsa_circ_0088212-mediated miR-520 h/APOA1 axis inhibits osteosarcoma progression |
| title_sort | hsa circ 0088212 mediated mir 520 h apoa1 axis inhibits osteosarcoma progression |
| topic | cirRNA miRNA Sponge Proliferation Osteosarcoma |
| url | http://www.sciencedirect.com/science/article/pii/S1936523321002114 |
| work_keys_str_mv | AT fengliu hsacirc0088212mediatedmir520hapoa1axisinhibitsosteosarcomaprogression AT xiangyangzhang hsacirc0088212mediatedmir520hapoa1axisinhibitsosteosarcomaprogression AT feiwu hsacirc0088212mediatedmir520hapoa1axisinhibitsosteosarcomaprogression AT haopeng hsacirc0088212mediatedmir520hapoa1axisinhibitsosteosarcomaprogression |