miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway
Abstract Background The most common malignant type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The expression levels of hyaluronan-mediated motility receptor (HMMR) in many tumor types are significantly elevated. HMMR is closely associated with tumor-related progression, treatment r...
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2025-01-01
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| Series: | Journal of Translational Medicine |
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| Online Access: | https://doi.org/10.1186/s12967-024-05988-w |
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| author | Xinyang Niu Dingheng Lu Weitao Zhan Jiazhu Sun Yuxiao Li Yuchen Shi Kai Yu Suyuelin Huang Xueyou Ma Xiaoyan Liu Ben Liu |
| author_facet | Xinyang Niu Dingheng Lu Weitao Zhan Jiazhu Sun Yuxiao Li Yuchen Shi Kai Yu Suyuelin Huang Xueyou Ma Xiaoyan Liu Ben Liu |
| author_sort | Xinyang Niu |
| collection | DOAJ |
| description | Abstract Background The most common malignant type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The expression levels of hyaluronan-mediated motility receptor (HMMR) in many tumor types are significantly elevated. HMMR is closely associated with tumor-related progression, treatment resistance, and poor prognosis, and has yet to be fully investigated in terms of its expression patterns and molecular mechanisms of action in ccRCC. Further research is imperative to elucidate these aspects. Methods We used The Cancer Genome Atlas (TCGA) database to preliminarily investigate HMMR expression and function in ccRCC and the data for 19 samples from the NCBI GEO database (GSE207493) for single-cell analysis. We assessed the differential expression level of HMMR between ccRCC cancerous tissues and their matched non-tumor tissues. Subsequently, a series of in vivo and in vitro experiments were designed to elucidate the biological function of HMMR in ccRCC, including Transwell assays, CCK-8 assays, clone formation assays and subcutaneous xenograft experiments in nude mice. Through bioinformatics analysis, we identified potential microRNAs (miRNAs) that may regulate HMMR, as well as the possible signaling pathways involved. Finally, we conducted a series of cellular functional experiments to validate our hypotheses regarding the HMMR axis. Results HMMR expression was significantly up-regulated in tumor tissues of ccRCC patients, and elevated HMMR expression level showed a strong correlation with ccRCC progression and adverse prognoses of patients. Knocking down HMMR inhibited the proliferative and migratory abilities of ccRCC cells, while its overexpression amplified these oncogenic properties. In nude mice model, reduced HMMR expression inhibited ccRCC tumor proliferation in vivo. Furthermore, overexpression of an upstream transcriptional regulator, miR-9-5p, effectively downregulated HMMR expression and thus impeded ccRCC cells proliferation and migration. HMMR might influence ccRCC growth via the Epithelial-Mesenchymal Transition (EMT) pathway and the Janus Kinase 1/Signal Transducer and Activator of Transcription 1 (JAK1/STAT1) pathway. Conclusions HMMR is overexpressed in ccRCC, and there is a significant link between high HMMR expression and tumor progression, as well as poor patient prognosis. Specifically, HMMR could be targeted and inhibited by miR-9-5p and might modulate the tumorigenesis and progression of ccRCC through both EMT and JAK1/STAT1 signaling pathway. |
| format | Article |
| id | doaj-art-6df79e5ac5744723acee101a6c78722a |
| institution | Kabale University |
| issn | 1479-5876 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
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| series | Journal of Translational Medicine |
| spelling | doaj-art-6df79e5ac5744723acee101a6c78722a2025-01-12T12:37:49ZengBMCJournal of Translational Medicine1479-58762025-01-0123111710.1186/s12967-024-05988-wmiR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathwayXinyang Niu0Dingheng Lu1Weitao Zhan2Jiazhu Sun3Yuxiao Li4Yuchen Shi5Kai Yu6Suyuelin Huang7Xueyou Ma8Xiaoyan Liu9Ben Liu10Department of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Pathology, The First Affiliated Hospital, Zhejiang University School of MedicineDepartment of Urology, The First Affiliated Hospital, Zhejiang University School of MedicineAbstract Background The most common malignant type of kidney cancer is clear cell renal cell carcinoma (ccRCC). The expression levels of hyaluronan-mediated motility receptor (HMMR) in many tumor types are significantly elevated. HMMR is closely associated with tumor-related progression, treatment resistance, and poor prognosis, and has yet to be fully investigated in terms of its expression patterns and molecular mechanisms of action in ccRCC. Further research is imperative to elucidate these aspects. Methods We used The Cancer Genome Atlas (TCGA) database to preliminarily investigate HMMR expression and function in ccRCC and the data for 19 samples from the NCBI GEO database (GSE207493) for single-cell analysis. We assessed the differential expression level of HMMR between ccRCC cancerous tissues and their matched non-tumor tissues. Subsequently, a series of in vivo and in vitro experiments were designed to elucidate the biological function of HMMR in ccRCC, including Transwell assays, CCK-8 assays, clone formation assays and subcutaneous xenograft experiments in nude mice. Through bioinformatics analysis, we identified potential microRNAs (miRNAs) that may regulate HMMR, as well as the possible signaling pathways involved. Finally, we conducted a series of cellular functional experiments to validate our hypotheses regarding the HMMR axis. Results HMMR expression was significantly up-regulated in tumor tissues of ccRCC patients, and elevated HMMR expression level showed a strong correlation with ccRCC progression and adverse prognoses of patients. Knocking down HMMR inhibited the proliferative and migratory abilities of ccRCC cells, while its overexpression amplified these oncogenic properties. In nude mice model, reduced HMMR expression inhibited ccRCC tumor proliferation in vivo. Furthermore, overexpression of an upstream transcriptional regulator, miR-9-5p, effectively downregulated HMMR expression and thus impeded ccRCC cells proliferation and migration. HMMR might influence ccRCC growth via the Epithelial-Mesenchymal Transition (EMT) pathway and the Janus Kinase 1/Signal Transducer and Activator of Transcription 1 (JAK1/STAT1) pathway. Conclusions HMMR is overexpressed in ccRCC, and there is a significant link between high HMMR expression and tumor progression, as well as poor patient prognosis. Specifically, HMMR could be targeted and inhibited by miR-9-5p and might modulate the tumorigenesis and progression of ccRCC through both EMT and JAK1/STAT1 signaling pathway.https://doi.org/10.1186/s12967-024-05988-wccRCCHMMRmiR-9-5pEMTJAK1/STAT1 |
| spellingShingle | Xinyang Niu Dingheng Lu Weitao Zhan Jiazhu Sun Yuxiao Li Yuchen Shi Kai Yu Suyuelin Huang Xueyou Ma Xiaoyan Liu Ben Liu miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway Journal of Translational Medicine ccRCC HMMR miR-9-5p EMT JAK1/STAT1 |
| title | miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway |
| title_full | miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway |
| title_fullStr | miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway |
| title_full_unstemmed | miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway |
| title_short | miR-9-5p/HMMR regulates the tumorigenesis and progression of clear cell renal cell carcinoma through EMT and JAK1/STAT1 signaling pathway |
| title_sort | mir 9 5p hmmr regulates the tumorigenesis and progression of clear cell renal cell carcinoma through emt and jak1 stat1 signaling pathway |
| topic | ccRCC HMMR miR-9-5p EMT JAK1/STAT1 |
| url | https://doi.org/10.1186/s12967-024-05988-w |
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