Long non-coding RNA OSTM1-AS1 promotes renal cell carcinoma progression by sponging miR-491-5p and upregulating MMP-9
Abstract Long noncoding RNAs (lncRNAs) have been recognized as essential regulators in various human malignancies. Hundreds of lncRNAs were known to be abnormally expressed in renal cell carcinoma (RCC) through a lncRNA expression microarray, among which lncRNA OSTM1 antisense RNA 1(OSTM1-AS1) was r...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-024-83154-4 |
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| author | Jun-Feng Chen Sha-Zhou Ye Ke-Jie Wang Xiang-yu Meng Bin-bin Yang Ke Rong Wu Qi Ma |
| author_facet | Jun-Feng Chen Sha-Zhou Ye Ke-Jie Wang Xiang-yu Meng Bin-bin Yang Ke Rong Wu Qi Ma |
| author_sort | Jun-Feng Chen |
| collection | DOAJ |
| description | Abstract Long noncoding RNAs (lncRNAs) have been recognized as essential regulators in various human malignancies. Hundreds of lncRNAs were known to be abnormally expressed in renal cell carcinoma (RCC) through a lncRNA expression microarray, among which lncRNA OSTM1 antisense RNA 1(OSTM1-AS1) was revealed as one of the most abundant lncRNAs. However, the function of OSTM1-AS1 in RCC remains unknown. Here, we examined OSTM1-AS1 functional roles and mechanism in RCC development. OSTM1-AS1 expression was significantly highly expressed among RCC tissue specimens and cell lines. Functionally, OSTM1-AS1 knockdown significantly suppressed cell proliferation, migration along with metastasis of RCC cells. Mechanistically, miR-491-5p was targeted via OSTM1-AS1, and down-regulation of miR-491-5p reversed OSTM1-AS1 knockdown impact on RCC migration and invasion. MMP-9 was targeted via miR-491-5p, and MMP-9 overexpression reversed miR-491-5p or OSTM1-AS1 knockdown impact on cell migration and invasion. MMP-9 abundance was decreased by OSTM1-AS1 silence, that was reduced by miR-491-5p deficiency. Importantly, our investigation revealed that OSTM1-AS1 has the ability to interact with miR-491-5p, thereby increasing the MMP-9 expression. The in vivo trial demonstrated that OSTM1-AS1 suppression resulted in tumor growth inhibition among nude mice. In summary, our findings indicate, for the first time, at least to the best of our knowledge, that OSTM1-AS1 serves as an oncogene among RCC by promoting proliferation, invasion, and metastasis through its targeting of the miR-491-5p/MMP9 axis. Therefore, this axis could represent a promising alternative therapeutic target for RCC treatment. |
| format | Article |
| id | doaj-art-e0f19a7c2856410d97f3e563c6240cdf |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-e0f19a7c2856410d97f3e563c6240cdf2025-01-05T12:23:24ZengNature PortfolioScientific Reports2045-23222025-01-0115111410.1038/s41598-024-83154-4Long non-coding RNA OSTM1-AS1 promotes renal cell carcinoma progression by sponging miR-491-5p and upregulating MMP-9Jun-Feng Chen0Sha-Zhou Ye1Ke-Jie Wang2Xiang-yu Meng3Bin-bin Yang4Ke Rong Wu5Qi Ma6Translational Research Laboratory for Urology, The Key Laboratory of Ningbo City, Ningbo Clinical Research Center for Urological Disease, Comprehensive Urogenital Cancer Center, The First Affiliated Hospital of Ningbo UniversityTranslational Research Laboratory for Urology, The Key Laboratory of Ningbo City, Ningbo Clinical Research Center for Urological Disease, Comprehensive Urogenital Cancer Center, The First Affiliated Hospital of Ningbo UniversityTranslational Research Laboratory for Urology, The Key Laboratory of Ningbo City, Ningbo Clinical Research Center for Urological Disease, Comprehensive Urogenital Cancer Center, The First Affiliated Hospital of Ningbo UniversityTranslational Research Laboratory for Urology, The Key Laboratory of Ningbo City, Ningbo Clinical Research Center for Urological Disease, Comprehensive Urogenital Cancer Center, The First Affiliated Hospital of Ningbo UniversityDepartment of Urology, The First Affiliated Hospital of Ningbo UniversityTranslational Research Laboratory for Urology, The Key Laboratory of Ningbo City, Ningbo Clinical Research Center for Urological Disease, Comprehensive Urogenital Cancer Center, The First Affiliated Hospital of Ningbo UniversityTranslational Research Laboratory for Urology, The Key Laboratory of Ningbo City, Ningbo Clinical Research Center for Urological Disease, Comprehensive Urogenital Cancer Center, The First Affiliated Hospital of Ningbo UniversityAbstract Long noncoding RNAs (lncRNAs) have been recognized as essential regulators in various human malignancies. Hundreds of lncRNAs were known to be abnormally expressed in renal cell carcinoma (RCC) through a lncRNA expression microarray, among which lncRNA OSTM1 antisense RNA 1(OSTM1-AS1) was revealed as one of the most abundant lncRNAs. However, the function of OSTM1-AS1 in RCC remains unknown. Here, we examined OSTM1-AS1 functional roles and mechanism in RCC development. OSTM1-AS1 expression was significantly highly expressed among RCC tissue specimens and cell lines. Functionally, OSTM1-AS1 knockdown significantly suppressed cell proliferation, migration along with metastasis of RCC cells. Mechanistically, miR-491-5p was targeted via OSTM1-AS1, and down-regulation of miR-491-5p reversed OSTM1-AS1 knockdown impact on RCC migration and invasion. MMP-9 was targeted via miR-491-5p, and MMP-9 overexpression reversed miR-491-5p or OSTM1-AS1 knockdown impact on cell migration and invasion. MMP-9 abundance was decreased by OSTM1-AS1 silence, that was reduced by miR-491-5p deficiency. Importantly, our investigation revealed that OSTM1-AS1 has the ability to interact with miR-491-5p, thereby increasing the MMP-9 expression. The in vivo trial demonstrated that OSTM1-AS1 suppression resulted in tumor growth inhibition among nude mice. In summary, our findings indicate, for the first time, at least to the best of our knowledge, that OSTM1-AS1 serves as an oncogene among RCC by promoting proliferation, invasion, and metastasis through its targeting of the miR-491-5p/MMP9 axis. Therefore, this axis could represent a promising alternative therapeutic target for RCC treatment.https://doi.org/10.1038/s41598-024-83154-4lncRNAsOSTM1-AS1miR-491-5pMMP-9Cell migrationCell invasion |
| spellingShingle | Jun-Feng Chen Sha-Zhou Ye Ke-Jie Wang Xiang-yu Meng Bin-bin Yang Ke Rong Wu Qi Ma Long non-coding RNA OSTM1-AS1 promotes renal cell carcinoma progression by sponging miR-491-5p and upregulating MMP-9 Scientific Reports lncRNAs OSTM1-AS1 miR-491-5p MMP-9 Cell migration Cell invasion |
| title | Long non-coding RNA OSTM1-AS1 promotes renal cell carcinoma progression by sponging miR-491-5p and upregulating MMP-9 |
| title_full | Long non-coding RNA OSTM1-AS1 promotes renal cell carcinoma progression by sponging miR-491-5p and upregulating MMP-9 |
| title_fullStr | Long non-coding RNA OSTM1-AS1 promotes renal cell carcinoma progression by sponging miR-491-5p and upregulating MMP-9 |
| title_full_unstemmed | Long non-coding RNA OSTM1-AS1 promotes renal cell carcinoma progression by sponging miR-491-5p and upregulating MMP-9 |
| title_short | Long non-coding RNA OSTM1-AS1 promotes renal cell carcinoma progression by sponging miR-491-5p and upregulating MMP-9 |
| title_sort | long non coding rna ostm1 as1 promotes renal cell carcinoma progression by sponging mir 491 5p and upregulating mmp 9 |
| topic | lncRNAs OSTM1-AS1 miR-491-5p MMP-9 Cell migration Cell invasion |
| url | https://doi.org/10.1038/s41598-024-83154-4 |
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