miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos
Background We aimed to investigate the effects of miR-34a-5p on c-fos regulation mediating the malignant behaviors of SH-SY5Y cells infected with Kaposi’s sarcoma-associated herpesvirus (KSHV). Methods The KSHV-infected (SK-RG) and uninfected SH-SY5Y parent cells were compared for differentially exp...
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| Format: | Article |
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PeerJ Inc.
2022-04-01
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| Online Access: | https://peerj.com/articles/13233.pdf |
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| author | Shuyuan Wu Zhaofu Wu Huiling Xu Jinli Zhang Wenyi Gu Xiaohua Tan Zemin Pan Dongdong Cao Dongmei Li Lei Yang Dongmei Li Yuanming Pan |
| author_facet | Shuyuan Wu Zhaofu Wu Huiling Xu Jinli Zhang Wenyi Gu Xiaohua Tan Zemin Pan Dongdong Cao Dongmei Li Lei Yang Dongmei Li Yuanming Pan |
| author_sort | Shuyuan Wu |
| collection | DOAJ |
| description | Background We aimed to investigate the effects of miR-34a-5p on c-fos regulation mediating the malignant behaviors of SH-SY5Y cells infected with Kaposi’s sarcoma-associated herpesvirus (KSHV). Methods The KSHV-infected (SK-RG) and uninfected SH-SY5Y parent cells were compared for differentially expressed miRNAs using transcriptome sequencing. Then miR-34a-5p was upregulated in SK-RG cells by the miRNA mimics transfection. Cell proliferation ability was determined by MTT and plate clone assays. The cell cycle was assessed by flow cytometry analysis, and CDK4, CDK6, cyclin D1 levels were determined by Western blot analysis. The migration behavior was detected by wound healing and transwell assays. The protein levels of MMP2 and MMP9 were measured by Western blot analysis. The regulation of c-fos by miR-34a-5p was detected by the dual-luciferase reporter gene assay. Rescue assays were carried out by upregulating c-fos in miR-34a-5p-overexpressing SK-RG cells. KSHV DNA copy numbers and relative virus gene expressions were detected. Xenograft tumor experiments and immunohistochemistry assays were further used to detect the effects of miR-34a-5p. Results miR-34a-5p was lower in SK-RG cells. Restoration of miR-34a-5p decreased cell proliferation and migration, leading to a G1 cell cycle arrest and down-regulation of CDK4/6, cyclin D1, MMP2, MMP9. KSHV copy number and expression of virus gene including latency-associated nuclear antigen (LANA), replication and transcription activator (RTA), open reading frame (K8.1), and KSHV G protein-coupled receptor (v-GPCR) were also reduced. Furthermore, c-fos is the target of miR-34a-5p, while enhanced c-fos weakened cellular behaviors of miR-34a-5p-overexpressing cells. Xenograft experiments and immunohistochemistry assays showed that miR-34a-5p inhibited tumor growth and virus gene expression. Conclusion Upregulated miR-34a-5p in KSHV-infected SH-SY5Y cells suppressed cell proliferation and migration through down-regulating c-fos. miR-34a-5p was a candidate molecular drug for KSHV-infected neuronal cells. |
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| spelling | doaj.art-01e31310fb6f42bca71353dc1b34843a2023-12-02T21:52:16ZengPeerJ Inc.PeerJ2167-83592022-04-0110e1323310.7717/peerj.13233miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fosShuyuan Wu0Zhaofu Wu1Huiling Xu2Jinli Zhang3Wenyi Gu4Xiaohua Tan5Zemin Pan6Dongdong Cao7Dongmei Li8Lei Yang9Dongmei Li10Yuanming Pan11Key Laboratory of Xinjiang Endemic and Ethnic Diseases/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang, ChinaAustralian Institute for Bioengineering and Nanotechnology (AIBN), University of Queensland (UQ), St Lucia, Brisbane, AustraliaSchool of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang, ChinaSchool of Medicine, Hangzhou Normal University, Hangzhou, Zhejiang, ChinaKey Laboratory of Xinjiang Endemic and Ethnic Diseases/NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, School of Medicine, Shihezi University, Shihezi, Xinjiang, ChinaDepartment of Cellular and Molecular Biology, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, Beijing, ChinaBackground We aimed to investigate the effects of miR-34a-5p on c-fos regulation mediating the malignant behaviors of SH-SY5Y cells infected with Kaposi’s sarcoma-associated herpesvirus (KSHV). Methods The KSHV-infected (SK-RG) and uninfected SH-SY5Y parent cells were compared for differentially expressed miRNAs using transcriptome sequencing. Then miR-34a-5p was upregulated in SK-RG cells by the miRNA mimics transfection. Cell proliferation ability was determined by MTT and plate clone assays. The cell cycle was assessed by flow cytometry analysis, and CDK4, CDK6, cyclin D1 levels were determined by Western blot analysis. The migration behavior was detected by wound healing and transwell assays. The protein levels of MMP2 and MMP9 were measured by Western blot analysis. The regulation of c-fos by miR-34a-5p was detected by the dual-luciferase reporter gene assay. Rescue assays were carried out by upregulating c-fos in miR-34a-5p-overexpressing SK-RG cells. KSHV DNA copy numbers and relative virus gene expressions were detected. Xenograft tumor experiments and immunohistochemistry assays were further used to detect the effects of miR-34a-5p. Results miR-34a-5p was lower in SK-RG cells. Restoration of miR-34a-5p decreased cell proliferation and migration, leading to a G1 cell cycle arrest and down-regulation of CDK4/6, cyclin D1, MMP2, MMP9. KSHV copy number and expression of virus gene including latency-associated nuclear antigen (LANA), replication and transcription activator (RTA), open reading frame (K8.1), and KSHV G protein-coupled receptor (v-GPCR) were also reduced. Furthermore, c-fos is the target of miR-34a-5p, while enhanced c-fos weakened cellular behaviors of miR-34a-5p-overexpressing cells. Xenograft experiments and immunohistochemistry assays showed that miR-34a-5p inhibited tumor growth and virus gene expression. Conclusion Upregulated miR-34a-5p in KSHV-infected SH-SY5Y cells suppressed cell proliferation and migration through down-regulating c-fos. miR-34a-5p was a candidate molecular drug for KSHV-infected neuronal cells.https://peerj.com/articles/13233.pdfmiR-34a-5pKaposi’s sarcoma–associated herpesvirusc-fosProliferationMigration |
| spellingShingle | Shuyuan Wu Zhaofu Wu Huiling Xu Jinli Zhang Wenyi Gu Xiaohua Tan Zemin Pan Dongdong Cao Dongmei Li Lei Yang Dongmei Li Yuanming Pan miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos PeerJ miR-34a-5p Kaposi’s sarcoma–associated herpesvirus c-fos Proliferation Migration |
| title | miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos |
| title_full | miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos |
| title_fullStr | miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos |
| title_full_unstemmed | miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos |
| title_short | miR-34a-5p inhibits the malignant progression of KSHV-infected SH-SY5Y cells by targeting c-fos |
| title_sort | mir 34a 5p inhibits the malignant progression of kshv infected sh sy5y cells by targeting c fos |
| topic | miR-34a-5p Kaposi’s sarcoma–associated herpesvirus c-fos Proliferation Migration |
| url | https://peerj.com/articles/13233.pdf |
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