LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer
Abstract Objective LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resis...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-05-01
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| Series: | Journal of Ovarian Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13048-021-00807-y |
| _version_ | 1797971113470328832 |
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| author | Li-yuan Feng Yong-zhi Huang Wei Zhang Li Li |
| author_facet | Li-yuan Feng Yong-zhi Huang Wei Zhang Li Li |
| author_sort | Li-yuan Feng |
| collection | DOAJ |
| description | Abstract Objective LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resistance and prognosis of ovarian cancer was confirmed in experiments. Methods Multiple databases have performed the bioinformatics analysis of methylation and transcription factor binding site (TFBS) on the promoter region of LAMA3 gene. Pyrosequencing detected the methylation of LAMA3. QRT-PCR and immunohistochemistry detected the expression of LAMA3. Real Time Cell Analyzer (RTCA) detects changes in cell proliferation, migration and invasion ability. Flow cytometry was used to detect apoptosis. Results CPG islands of 176 bp, 134 bp, 125 bp and 531 bp were predicted in the promoter region of LAMA3 gene. The 4 prediction results are basically overlapped. 7 transcription factor binding sites were predicted, and the one with the highest score was on the predicted CpG island located in the proximal promoter region. LAMA3 hypermethylation and low expression are both associated with chemotherapy resistance and poor prognosis in ovarian cancer. LAMA3 methylation was negatively correlated with expression. After upregulation of LAMA3, the proliferation ability of chemoresistant ovarian cancer cell decreased, while the ability of apoptosis, invasion and migration increased. Conclusion LAMA3 hypermethylation is associated with chemotherapy resistance and poor prognosis. As a typical CpG island gene, LAMA3(cg20937934) and LAMA3(cg13270625) hypermethylation is negatively correlated with low expression. LAMA3 promotes the invasion, migration and apoptosis of SKOV3DDP. In the future, the mechanism of LAMA3 methylation in ovarian cancer will need to be further studied. |
| first_indexed | 2024-04-11T03:26:27Z |
| format | Article |
| id | doaj.art-0093d49fc99c41c08f7ba940f08bb057 |
| institution | Directory Open Access Journal |
| issn | 1757-2215 |
| language | English |
| last_indexed | 2024-04-11T03:26:27Z |
| publishDate | 2021-05-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Ovarian Research |
| spelling | doaj.art-0093d49fc99c41c08f7ba940f08bb0572023-01-02T07:10:05ZengBMCJournal of Ovarian Research1757-22152021-05-0114111010.1186/s13048-021-00807-yLAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancerLi-yuan Feng0Yong-zhi Huang1Wei Zhang2Li Li3Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of EducationDepartment of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of EducationDepartment of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of EducationDepartment of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of EducationAbstract Objective LAMA3 is a widely studied methylated gene in multiple tumors, but the relationship between chemotherapy resistance in ovarian cancer is unclear. In this study, LAMA3 methylation was predicted by bioinformatics, and the ability of LAMA3 methylation to predict the chemotherapy resistance and prognosis of ovarian cancer was confirmed in experiments. Methods Multiple databases have performed the bioinformatics analysis of methylation and transcription factor binding site (TFBS) on the promoter region of LAMA3 gene. Pyrosequencing detected the methylation of LAMA3. QRT-PCR and immunohistochemistry detected the expression of LAMA3. Real Time Cell Analyzer (RTCA) detects changes in cell proliferation, migration and invasion ability. Flow cytometry was used to detect apoptosis. Results CPG islands of 176 bp, 134 bp, 125 bp and 531 bp were predicted in the promoter region of LAMA3 gene. The 4 prediction results are basically overlapped. 7 transcription factor binding sites were predicted, and the one with the highest score was on the predicted CpG island located in the proximal promoter region. LAMA3 hypermethylation and low expression are both associated with chemotherapy resistance and poor prognosis in ovarian cancer. LAMA3 methylation was negatively correlated with expression. After upregulation of LAMA3, the proliferation ability of chemoresistant ovarian cancer cell decreased, while the ability of apoptosis, invasion and migration increased. Conclusion LAMA3 hypermethylation is associated with chemotherapy resistance and poor prognosis. As a typical CpG island gene, LAMA3(cg20937934) and LAMA3(cg13270625) hypermethylation is negatively correlated with low expression. LAMA3 promotes the invasion, migration and apoptosis of SKOV3DDP. In the future, the mechanism of LAMA3 methylation in ovarian cancer will need to be further studied.https://doi.org/10.1186/s13048-021-00807-yOvarian cancerChemoresistanceLAMA3 methylationPrognosis |
| spellingShingle | Li-yuan Feng Yong-zhi Huang Wei Zhang Li Li LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer Journal of Ovarian Research Ovarian cancer Chemoresistance LAMA3 methylation Prognosis |
| title | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
| title_full | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
| title_fullStr | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
| title_full_unstemmed | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
| title_short | LAMA3 DNA methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
| title_sort | lama3 dna methylation and transcriptome changes associated with chemotherapy resistance in ovarian cancer |
| topic | Ovarian cancer Chemoresistance LAMA3 methylation Prognosis |
| url | https://doi.org/10.1186/s13048-021-00807-y |
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