LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141
Osteosarcoma (OS) is one of the most common types of malignant tumors characterized by uncontrolled proliferation ability and acquired drug resistance. The previous study indicated that lncRNA KRAL participated in the reversal of 5-FU resistance in liver cancer, but it remains unclear whether lncRNA...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2020-09-01
|
| Series: | European Journal of Inflammation |
| Online Access: | https://doi.org/10.1177/2058739220959904 |
| _version_ | 1819011818769612800 |
|---|---|
| author | Jingwei Cai Xiaohui Chen Fei Ma Jun Qian Ming Niu Yuzhen Gao Junwei Li Xiaoqiang Ren |
| author_facet | Jingwei Cai Xiaohui Chen Fei Ma Jun Qian Ming Niu Yuzhen Gao Junwei Li Xiaoqiang Ren |
| author_sort | Jingwei Cai |
| collection | DOAJ |
| description | Osteosarcoma (OS) is one of the most common types of malignant tumors characterized by uncontrolled proliferation ability and acquired drug resistance. The previous study indicated that lncRNA KRAL participated in the reversal of 5-FU resistance in liver cancer, but it remains unclear whether lncRNA KRAL involved in doxorubicin (DOX) resistance of osteosarcoma. The expression of lncRNA KRAL and MicroRNAs-141 (miR-141) were detected by RT-qPCR experiment. Also, we used the plasmids transfection to construct the lncRNA KRAL overexpressed OS cell lines. Subsequently, the cell proliferation ability and the sensitivity to DOX in OS cells upon upregulating lncRNA KRAL expression were analyzed via CCK-8 and EDU assay, while western blotting experiment was performed to detect the regulatory mechanism. We found that lncRNA KRAL was downregulated in OS tissues, and the OS patients with OS patients with lower expression of lncRNA KRAL were more likely to have advanced Enneking stage, larger tumor size and distant metastasis. Subsequently, we discovered that upregulation of lncRNA KRAL could inhibit cell proliferation and increase the sensitivity to DOX of OS cells. Interestingly, the western blot results showed that over-expression of lncRNA KRAL could lead to down-expression of P-gp protein and reversal of Epithelial–mesenchymal transition (EMT) pathway. Furthermore, we identified miR-141 as the downstream target gene of lncRNA KRAL, which was further confirmed by the luciferase reporter assay. More importantly, our data demonstrated that addition of miR-141 could reverse cell proliferation and drug sensitivity of lncRNA KRAL-overexpressed OS cells. LncRNA KRAL could suppress cell growth and increases sensitivity to DOX in OS cells by sponging miR-141. |
| first_indexed | 2024-12-21T01:34:12Z |
| format | Article |
| id | doaj.art-7371238c35b548f19062dd70ec065c3b |
| institution | Directory Open Access Journal |
| issn | 2058-7392 |
| language | English |
| last_indexed | 2024-12-21T01:34:12Z |
| publishDate | 2020-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | European Journal of Inflammation |
| spelling | doaj.art-7371238c35b548f19062dd70ec065c3b2022-12-21T19:20:17ZengSAGE PublishingEuropean Journal of Inflammation2058-73922020-09-011810.1177/2058739220959904LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141Jingwei Cai0Xiaohui Chen1Fei Ma2Jun Qian3Ming Niu4Yuzhen Gao5Junwei Li6Xiaoqiang Ren7Department of Orthopedics, People’s Hospital of Ganzhou District, Zhangye, PR ChinaDepartment of Anesthesiology, Gansu Provincial Hospital, Gansu Province, PR ChinaDepartment of Orthopedics, People’s Hospital of Ganzhou District, Zhangye, PR ChinaDepartment of Orthopedics, Zhangye People’s Hospital Affiliated to Hexi University, Zhangye, PR ChinaDepartment of Orthopedics, People’s Hospital of Ganzhou District, Zhangye, PR ChinaDepartment of Orthopedics, People’s Hospital of Ganzhou District, Zhangye, PR ChinaDepartment of Orthopedics, People’s Hospital of Ganzhou District, Zhangye, PR ChinaDepartment of Orthopedics, Zhangye People’s Hospital Affiliated to Hexi University, Zhangye, PR ChinaOsteosarcoma (OS) is one of the most common types of malignant tumors characterized by uncontrolled proliferation ability and acquired drug resistance. The previous study indicated that lncRNA KRAL participated in the reversal of 5-FU resistance in liver cancer, but it remains unclear whether lncRNA KRAL involved in doxorubicin (DOX) resistance of osteosarcoma. The expression of lncRNA KRAL and MicroRNAs-141 (miR-141) were detected by RT-qPCR experiment. Also, we used the plasmids transfection to construct the lncRNA KRAL overexpressed OS cell lines. Subsequently, the cell proliferation ability and the sensitivity to DOX in OS cells upon upregulating lncRNA KRAL expression were analyzed via CCK-8 and EDU assay, while western blotting experiment was performed to detect the regulatory mechanism. We found that lncRNA KRAL was downregulated in OS tissues, and the OS patients with OS patients with lower expression of lncRNA KRAL were more likely to have advanced Enneking stage, larger tumor size and distant metastasis. Subsequently, we discovered that upregulation of lncRNA KRAL could inhibit cell proliferation and increase the sensitivity to DOX of OS cells. Interestingly, the western blot results showed that over-expression of lncRNA KRAL could lead to down-expression of P-gp protein and reversal of Epithelial–mesenchymal transition (EMT) pathway. Furthermore, we identified miR-141 as the downstream target gene of lncRNA KRAL, which was further confirmed by the luciferase reporter assay. More importantly, our data demonstrated that addition of miR-141 could reverse cell proliferation and drug sensitivity of lncRNA KRAL-overexpressed OS cells. LncRNA KRAL could suppress cell growth and increases sensitivity to DOX in OS cells by sponging miR-141.https://doi.org/10.1177/2058739220959904 |
| spellingShingle | Jingwei Cai Xiaohui Chen Fei Ma Jun Qian Ming Niu Yuzhen Gao Junwei Li Xiaoqiang Ren LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141 European Journal of Inflammation |
| title | LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141 |
| title_full | LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141 |
| title_fullStr | LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141 |
| title_full_unstemmed | LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141 |
| title_short | LncRNA KRAL suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging microRNAs-141 |
| title_sort | lncrna kral suppresses cell growth and increases sensitivity to doxorubicin in osteosarcoma cells by sponging micrornas 141 |
| url | https://doi.org/10.1177/2058739220959904 |
| work_keys_str_mv | AT jingweicai lncrnakralsuppressescellgrowthandincreasessensitivitytodoxorubicininosteosarcomacellsbyspongingmicrornas141 AT xiaohuichen lncrnakralsuppressescellgrowthandincreasessensitivitytodoxorubicininosteosarcomacellsbyspongingmicrornas141 AT feima lncrnakralsuppressescellgrowthandincreasessensitivitytodoxorubicininosteosarcomacellsbyspongingmicrornas141 AT junqian lncrnakralsuppressescellgrowthandincreasessensitivitytodoxorubicininosteosarcomacellsbyspongingmicrornas141 AT mingniu lncrnakralsuppressescellgrowthandincreasessensitivitytodoxorubicininosteosarcomacellsbyspongingmicrornas141 AT yuzhengao lncrnakralsuppressescellgrowthandincreasessensitivitytodoxorubicininosteosarcomacellsbyspongingmicrornas141 AT junweili lncrnakralsuppressescellgrowthandincreasessensitivitytodoxorubicininosteosarcomacellsbyspongingmicrornas141 AT xiaoqiangren lncrnakralsuppressescellgrowthandincreasessensitivitytodoxorubicininosteosarcomacellsbyspongingmicrornas141 |