Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling Pathway
Objective To explore the relationship of UHRF1 with the clinicopathological characteristics of colorectal cancer (CRC) patients, as well as the effects of lentivirus transfection overexpression and knockdown of UHRF1 on the proliferation, invasion, and migration of CRC cells and the possible signali...
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| Format: | Article |
| Language: | zho |
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Magazine House of Cancer Research on Prevention and Treatment
2023-11-01
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| Series: | Zhongliu Fangzhi Yanjiu |
| Subjects: | |
| Online Access: | http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0498 |
| _version_ | 1797401590129229824 |
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| author | CHEN Zhihua ZHENG Yan LIN Suyong CHEN Shaoqin |
| author_facet | CHEN Zhihua ZHENG Yan LIN Suyong CHEN Shaoqin |
| author_sort | CHEN Zhihua |
| collection | DOAJ |
| description | Objective To explore the relationship of UHRF1 with the clinicopathological characteristics of colorectal cancer (CRC) patients, as well as the effects of lentivirus transfection overexpression and knockdown of UHRF1 on the proliferation, invasion, and migration of CRC cells and the possible signaling pathways. Methods The expression of UHRF1 mRNA and protein in CRC tissues and adjacent tissues was detected by immunohistochemical staining and RT-PCR. The effects of the constructed UHRF1 overexpression- and knockdown-group cells on the expression of UHRF1, related molecules in the WNT signaling pathway, and MMPR9 were examined by Western blot and RT-PCR. EDU and Transwell assays were used to detect changes in the proliferation, migration, and invasion of CRC cells. Results (1) In the TCGA database and clinical data, the mRNA and protein expression levels of UHRF1 in CRC cancer tissues were significantly higher than those in adjacent normal tissues. UHRF1 expression was closely correlated with TNM stage, N stage, and M stage. Patients with low UHRF1 expression in TCGA had better 5-year OS and disease-specific survival. The area under the ROC curve of UHRF1 for predicting 1-, 3-, and 5-year OS were 0.634, 0.652, and 0.771, respectively. The 3-year OS in the clinical data also showed the same survival benefit. UHRF1 overexpression was a poor prognostic factor for CRC patients. (2) After UHRF1 overexpression, the expression of WNT3a, GSK3β, and MMP9 in SW480 cells significantly increased, whereas the expression of p-β-catenin decreased (P < 0.05). After UHRF1 knockdown, the expression of WNT3a, GSK3β, and MMP9 in HCT116 cells decreased, whereas the expression of p-β-catenin increased (P < 0.05). The "rescue" experiment with IWP-2 and HLY78 can produce consistent results. (3) Compared with the control group, the cell proliferation, migration, and invasion abilities of the UHRF1 overexpression group were enhanced. After IWP-2 treatment, the cell proliferation, migration, and invasion abilities were inhibited. Knockdown experiment exhibited the reverse results to overexpression experiment. Conclusion UHRF1 may play an important role in the occurrence and development of CRC. UHRF1 overexpression may be a poor prognostic factor for CRC patients. UHRF1 may affect the proliferation, migration, and invasion of CRC cells through the WNT/MMP9 signaling pathway. |
| first_indexed | 2024-03-09T02:12:26Z |
| format | Article |
| id | doaj.art-226d0f2440fc4c97ab6810c3407be588 |
| institution | Directory Open Access Journal |
| issn | 1000-8578 |
| language | zho |
| last_indexed | 2024-03-09T02:12:26Z |
| publishDate | 2023-11-01 |
| publisher | Magazine House of Cancer Research on Prevention and Treatment |
| record_format | Article |
| series | Zhongliu Fangzhi Yanjiu |
| spelling | doaj.art-226d0f2440fc4c97ab6810c3407be5882023-12-07T07:46:12ZzhoMagazine House of Cancer Research on Prevention and TreatmentZhongliu Fangzhi Yanjiu1000-85782023-11-0150111075108310.3971/j.issn.1000-8578.2023.23.04988578.2023.23.0498Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling PathwayCHEN Zhihua0ZHENG Yan1LIN Suyong2CHEN Shaoqin3Department of Gastrointestinal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaDepartment of Gastrointestinal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaDepartment of Gastrointestinal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaDepartment of Gastrointestinal Surgery, the First Affiliated Hospital of Fujian Medical University, Fuzhou 350005, ChinaObjective To explore the relationship of UHRF1 with the clinicopathological characteristics of colorectal cancer (CRC) patients, as well as the effects of lentivirus transfection overexpression and knockdown of UHRF1 on the proliferation, invasion, and migration of CRC cells and the possible signaling pathways. Methods The expression of UHRF1 mRNA and protein in CRC tissues and adjacent tissues was detected by immunohistochemical staining and RT-PCR. The effects of the constructed UHRF1 overexpression- and knockdown-group cells on the expression of UHRF1, related molecules in the WNT signaling pathway, and MMPR9 were examined by Western blot and RT-PCR. EDU and Transwell assays were used to detect changes in the proliferation, migration, and invasion of CRC cells. Results (1) In the TCGA database and clinical data, the mRNA and protein expression levels of UHRF1 in CRC cancer tissues were significantly higher than those in adjacent normal tissues. UHRF1 expression was closely correlated with TNM stage, N stage, and M stage. Patients with low UHRF1 expression in TCGA had better 5-year OS and disease-specific survival. The area under the ROC curve of UHRF1 for predicting 1-, 3-, and 5-year OS were 0.634, 0.652, and 0.771, respectively. The 3-year OS in the clinical data also showed the same survival benefit. UHRF1 overexpression was a poor prognostic factor for CRC patients. (2) After UHRF1 overexpression, the expression of WNT3a, GSK3β, and MMP9 in SW480 cells significantly increased, whereas the expression of p-β-catenin decreased (P < 0.05). After UHRF1 knockdown, the expression of WNT3a, GSK3β, and MMP9 in HCT116 cells decreased, whereas the expression of p-β-catenin increased (P < 0.05). The "rescue" experiment with IWP-2 and HLY78 can produce consistent results. (3) Compared with the control group, the cell proliferation, migration, and invasion abilities of the UHRF1 overexpression group were enhanced. After IWP-2 treatment, the cell proliferation, migration, and invasion abilities were inhibited. Knockdown experiment exhibited the reverse results to overexpression experiment. Conclusion UHRF1 may play an important role in the occurrence and development of CRC. UHRF1 overexpression may be a poor prognostic factor for CRC patients. UHRF1 may affect the proliferation, migration, and invasion of CRC cells through the WNT/MMP9 signaling pathway.http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0498colorectal canceruhrf1wnt/mmp9 signaling pathwayproliferationinvasion |
| spellingShingle | CHEN Zhihua ZHENG Yan LIN Suyong CHEN Shaoqin Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling Pathway Zhongliu Fangzhi Yanjiu colorectal cancer uhrf1 wnt/mmp9 signaling pathway proliferation invasion |
| title | Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling Pathway |
| title_full | Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling Pathway |
| title_fullStr | Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling Pathway |
| title_full_unstemmed | Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling Pathway |
| title_short | Inhibitory Effect of UHRF1 on Invasion and Migration of Colorectal Cancer Cells via WNT/MMP9 Signaling Pathway |
| title_sort | inhibitory effect of uhrf1 on invasion and migration of colorectal cancer cells via wnt mmp9 signaling pathway |
| topic | colorectal cancer uhrf1 wnt/mmp9 signaling pathway proliferation invasion |
| url | http://www.zlfzyj.com/EN/10.3971/j.issn.1000-8578.2023.23.0498 |
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