miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1
Abstract Background MicroRNAs (miRNAs) serve as important regulators of the tumorigenesis and progression of many human cancers. Therefore, we evaluated the biological function and underlying mechanism of miR-363 in clear cell renal cell carcinoma (ccRCC). Methods The expression of miR-363 in ccRCC...
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| Format: | Article |
| Language: | English |
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BMC
2020-06-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01313-9 |
| _version_ | 1818840710061752320 |
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| author | Yongpeng Xie Luyao Chen Yu Gao Xin Ma Weiyang He Yu Zhang Fan Zhang Yang Fan Liangyou Gu Pin Li Xu Zhang Xin Gou |
| author_facet | Yongpeng Xie Luyao Chen Yu Gao Xin Ma Weiyang He Yu Zhang Fan Zhang Yang Fan Liangyou Gu Pin Li Xu Zhang Xin Gou |
| author_sort | Yongpeng Xie |
| collection | DOAJ |
| description | Abstract Background MicroRNAs (miRNAs) serve as important regulators of the tumorigenesis and progression of many human cancers. Therefore, we evaluated the biological function and underlying mechanism of miR-363 in clear cell renal cell carcinoma (ccRCC). Methods The expression of miR-363 in ccRCC tissues compared with adjacent normal renal tissues was detected by quantitative real-time polymerase chain reaction, and the association between miR-363 levels and prognosis of ccRCC patients was analyzed. The candidate target gene of miR-363 was determined by in silico analysis and luciferase reporter assays. The effects of miR-363 on the proliferation, migration and invasion of ccRCC cells in vitro were determined by MTS assay, colony formation assay, Transwell assay and wound healing assay. We also investigated the roles of miR-363 in vivo by a xenograft tumour model. The mechanism of miR-363 on the proliferation, migration and invasion of ccRCC was determined by gain- and loss-of-function analyses. Results we demonstrated that miR-363 expression was obviously downregulated in ccRCC tissues and that reduced miR-363 expression was correlated with poor disease-free survival (DFS) in ccRCC patients after surgery. S1PR1 expression was inversely correlated with the level of miR-363 in human ccRCC samples. Luciferase reporter assays suggested that S1PR1 was a direct functional target of miR-363. miR-363 downregulated S1PR1 expression and suppressed the proliferation, migration and invasion abilities of ccRCC cells in vitro and suppressed xenograft tumour growth in vivo. Importantly, miR-363 exerted its biological function by inhibiting S1PR1 expression in ccRCC cells, leading to the repression of ERK activation. Moreover, we found that the levels of downstream effectors of ERK, including PDGF-A, PDGF-B, and epithelial-mesenchymal transition (EMT)-related genes, were decreased after miR-363 overexpression. Conclusions Our results suggest that miR-363 acts as a tumour suppressor by directly targeting S1PR1 in ccRCC and may be a potential new therapeutic target for ccRCC. |
| first_indexed | 2024-12-19T04:14:30Z |
| format | Article |
| id | doaj.art-992ca24a8aa44c61acb38ebd9d13f364 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-19T04:14:30Z |
| publishDate | 2020-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-992ca24a8aa44c61acb38ebd9d13f3642022-12-21T20:36:20ZengBMCCancer Cell International1475-28672020-06-0120111610.1186/s12935-020-01313-9miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1Yongpeng Xie0Luyao Chen1Yu Gao2Xin Ma3Weiyang He4Yu Zhang5Fan Zhang6Yang Fan7Liangyou Gu8Pin Li9Xu Zhang10Xin Gou11Department of Urology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Urology, The First Affiliated Hospital of Nanchang UniversityDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General HospitalDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General HospitalDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General HospitalDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General HospitalDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General HospitalDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General HospitalDepartment of Pediatric Urology, Bayi Children’s Hospital Affiliated to the Seventh Medical Center of Chinese PLA General HospitalDepartment of Urology, State Key Laboratory of Kidney Diseases, Chinese PLA General HospitalDepartment of Urology, The First Affiliated Hospital of Chongqing Medical UniversityAbstract Background MicroRNAs (miRNAs) serve as important regulators of the tumorigenesis and progression of many human cancers. Therefore, we evaluated the biological function and underlying mechanism of miR-363 in clear cell renal cell carcinoma (ccRCC). Methods The expression of miR-363 in ccRCC tissues compared with adjacent normal renal tissues was detected by quantitative real-time polymerase chain reaction, and the association between miR-363 levels and prognosis of ccRCC patients was analyzed. The candidate target gene of miR-363 was determined by in silico analysis and luciferase reporter assays. The effects of miR-363 on the proliferation, migration and invasion of ccRCC cells in vitro were determined by MTS assay, colony formation assay, Transwell assay and wound healing assay. We also investigated the roles of miR-363 in vivo by a xenograft tumour model. The mechanism of miR-363 on the proliferation, migration and invasion of ccRCC was determined by gain- and loss-of-function analyses. Results we demonstrated that miR-363 expression was obviously downregulated in ccRCC tissues and that reduced miR-363 expression was correlated with poor disease-free survival (DFS) in ccRCC patients after surgery. S1PR1 expression was inversely correlated with the level of miR-363 in human ccRCC samples. Luciferase reporter assays suggested that S1PR1 was a direct functional target of miR-363. miR-363 downregulated S1PR1 expression and suppressed the proliferation, migration and invasion abilities of ccRCC cells in vitro and suppressed xenograft tumour growth in vivo. Importantly, miR-363 exerted its biological function by inhibiting S1PR1 expression in ccRCC cells, leading to the repression of ERK activation. Moreover, we found that the levels of downstream effectors of ERK, including PDGF-A, PDGF-B, and epithelial-mesenchymal transition (EMT)-related genes, were decreased after miR-363 overexpression. Conclusions Our results suggest that miR-363 acts as a tumour suppressor by directly targeting S1PR1 in ccRCC and may be a potential new therapeutic target for ccRCC.http://link.springer.com/article/10.1186/s12935-020-01313-9miR-363ProliferationMigrationInvasionS1PR1Clear cell renal cell carcinoma |
| spellingShingle | Yongpeng Xie Luyao Chen Yu Gao Xin Ma Weiyang He Yu Zhang Fan Zhang Yang Fan Liangyou Gu Pin Li Xu Zhang Xin Gou miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1 Cancer Cell International miR-363 Proliferation Migration Invasion S1PR1 Clear cell renal cell carcinoma |
| title | miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1 |
| title_full | miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1 |
| title_fullStr | miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1 |
| title_full_unstemmed | miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1 |
| title_short | miR-363 suppresses the proliferation, migration and invasion of clear cell renal cell carcinoma by downregulating S1PR1 |
| title_sort | mir 363 suppresses the proliferation migration and invasion of clear cell renal cell carcinoma by downregulating s1pr1 |
| topic | miR-363 Proliferation Migration Invasion S1PR1 Clear cell renal cell carcinoma |
| url | http://link.springer.com/article/10.1186/s12935-020-01313-9 |
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