Hypermethylation of Single CpG Dinucleotides at the Promoter of CXCL13 Gene Promoting Cell Migration in Cervical Cancer
Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net..
BACKGROUND: Chemokine 13 (CXCL13) and its chemokine receptor 5 (CXCR5) are involved in the onset of various types of cancer. However, their role in cervical cancer (CC) remains unknown.
OBJECTIVE: To investigate the role of chemokine 13 (CXCL13) and its receptor in CC.
METHODS: The expression of CXCL13/CXCR5 and the infiltration of CXCR5+CD8+ T cells in CC, cervical intraepithelial neoplasia (CIN), normal cervical epithelial (NCE) tissues, and in CC cell lines were analysed and the associated clinical significance was determined. In vitro, CXCL13 overexpression and DNA methyltransferase inhibition (through S110) were used to investigate the biological function and the underlying mechanism that regulates CXCL13 expression. Tumor growth and liver metastasis were also evaluated in the xenogenous subcutaneously implant model.
RESULTS: CXCL13/CXCR5 expression levels and the infiltration of CXCR5+CD8+ T cells were significantly decreased in CC tissues compared with CIN and NCE tissues. CXCL13 downregulation was significantly correlated with the FIGO stages, lymph node metastasis, interstitial infiltration depth, and pathological grade. The overexpression of CXCL13 suppressed CC cell migration. CXCL13 downregulation was associated with hypermethylation in CC cell lines, and primary tumor biopsies. Furthermore, a CpG dinucleotide at the HIF-1a transcription factor motifs in the promoter element of CXCL13 was consistently methylated in CC cells and associated with HIF-1a. CXCL13 overexpression and S110 treatment dramatically repressed tumor growth and liver metastasis in the xenograft model; whereas it's low expression increased the risk of death in CC patients.
CONCLUSION: DNA methylation-dependent CXCL13 downregulation may promote cervical carcinogenesis and progression.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:20 |
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| Enthalten in: |
Current cancer drug targets - 20(2020), 5 vom: 03., Seite 355-363 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ma, Dong [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 02.08.2021 Date Revised 02.08.2021 published: Print Citation Status MEDLINE |
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| doi: |
10.2174/1568009620666200102123635 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM304992631 |
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| 100 | 1 | |a Ma, Dong |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Hypermethylation of Single CpG Dinucleotides at the Promoter of CXCL13 Gene Promoting Cell Migration in Cervical Cancer |
| 264 | 1 | |c 2020 | |
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| 500 | |a Date Revised 02.08.2021 | ||
| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright© Bentham Science Publishers; For any queries, please email at epubbenthamscience.net. | ||
| 520 | |a BACKGROUND: Chemokine 13 (CXCL13) and its chemokine receptor 5 (CXCR5) are involved in the onset of various types of cancer. However, their role in cervical cancer (CC) remains unknown | ||
| 520 | |a OBJECTIVE: To investigate the role of chemokine 13 (CXCL13) and its receptor in CC | ||
| 520 | |a METHODS: The expression of CXCL13/CXCR5 and the infiltration of CXCR5+CD8+ T cells in CC, cervical intraepithelial neoplasia (CIN), normal cervical epithelial (NCE) tissues, and in CC cell lines were analysed and the associated clinical significance was determined. In vitro, CXCL13 overexpression and DNA methyltransferase inhibition (through S110) were used to investigate the biological function and the underlying mechanism that regulates CXCL13 expression. Tumor growth and liver metastasis were also evaluated in the xenogenous subcutaneously implant model | ||
| 520 | |a RESULTS: CXCL13/CXCR5 expression levels and the infiltration of CXCR5+CD8+ T cells were significantly decreased in CC tissues compared with CIN and NCE tissues. CXCL13 downregulation was significantly correlated with the FIGO stages, lymph node metastasis, interstitial infiltration depth, and pathological grade. The overexpression of CXCL13 suppressed CC cell migration. CXCL13 downregulation was associated with hypermethylation in CC cell lines, and primary tumor biopsies. Furthermore, a CpG dinucleotide at the HIF-1a transcription factor motifs in the promoter element of CXCL13 was consistently methylated in CC cells and associated with HIF-1a. CXCL13 overexpression and S110 treatment dramatically repressed tumor growth and liver metastasis in the xenograft model; whereas it's low expression increased the risk of death in CC patients | ||
| 520 | |a CONCLUSION: DNA methylation-dependent CXCL13 downregulation may promote cervical carcinogenesis and progression | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a CXCL13 | |
| 650 | 4 | |a Cervical cancer | |
| 650 | 4 | |a HIF-1a | |
| 650 | 4 | |a liver metastasis | |
| 650 | 4 | |a methylation | |
| 650 | 4 | |a proliferation. | |
| 650 | 7 | |a Biomarkers, Tumor |2 NLM | |
| 650 | 7 | |a CXCL13 protein, human |2 NLM | |
| 650 | 7 | |a CXCR5 protein, human |2 NLM | |
| 650 | 7 | |a Chemokine CXCL13 |2 NLM | |
| 650 | 7 | |a Oligodeoxyribonucleotides |2 NLM | |
| 650 | 7 | |a Receptors, CXCR5 |2 NLM | |
| 700 | 1 | |a Fan, Shao-Bei |e verfasserin |4 aut | |
| 700 | 1 | |a Hua, Na |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Guo-Hua |e verfasserin |4 aut | |
| 700 | 1 | |a Chang, Quan |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Xiao |e verfasserin |4 aut | |
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