Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer
MicroRNAs (miRNAs) play an important role in gene regulation by degradation or translational inhibition of the targeted mRNAs. It has been experimentally shown that the way miRNAs interact with their targets can be used to explain the indirect interactions among their targets, i.e., competing endoge...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-02-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/23/4/2277 |
| _version_ | 1797479299778871296 |
|---|---|
| author | Tzy-Wei Huang Frank H. C. Cheng Ching-Cher Sanders Yan Yu-Ming Chuang Chien-Hong Cho Hung-Cheng Lai Shih-Feng Shieh Michael W. Y. Chan Je-Chiang Tsai |
| author_facet | Tzy-Wei Huang Frank H. C. Cheng Ching-Cher Sanders Yan Yu-Ming Chuang Chien-Hong Cho Hung-Cheng Lai Shih-Feng Shieh Michael W. Y. Chan Je-Chiang Tsai |
| author_sort | Tzy-Wei Huang |
| collection | DOAJ |
| description | MicroRNAs (miRNAs) play an important role in gene regulation by degradation or translational inhibition of the targeted mRNAs. It has been experimentally shown that the way miRNAs interact with their targets can be used to explain the indirect interactions among their targets, i.e., competing endogenous RNA (ceRNA). However, whether the protein translated from the targeted mRNAs can play any role in this ceRNA network has not been explored. Here we propose a deterministic model to demonstrate that in a network of one miRNA interacting with multiple-targeted mRNAs, the competition between miRNA-targeted mRNAs is not sufficient for the significant change of those targeted mRNA levels, while dramatic changes of these miRNA-targeted mRNAs require transcriptional inhibition of miRNA by its target proteins. When applied to estrogen receptor signaling pathways, the miR-193a targets E2F6 (a target of estrogen receptor), c-KIT (a marker for cancer stemness), and PBX1 (a transcriptional activator for immunosuppressive cytokine, IL-10) in ovarian cancer, such that epigenetic silencing of miR-193a by E2F6 protein is required for the significant change of c-KIT and PBX1 mRNA level for cancer stemness and immunoevasion, respectively, in ovarian cancer carcinogenesis |
| first_indexed | 2024-03-09T21:43:52Z |
| format | Article |
| id | doaj.art-310bd1ddcc7244758ac59c86549aa6e0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:43:52Z |
| publishDate | 2022-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-310bd1ddcc7244758ac59c86549aa6e02023-11-23T20:22:52ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234227710.3390/ijms23042277Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian CancerTzy-Wei Huang0Frank H. C. Cheng1Ching-Cher Sanders Yan2Yu-Ming Chuang3Chien-Hong Cho4Hung-Cheng Lai5Shih-Feng Shieh6Michael W. Y. Chan7Je-Chiang Tsai8Department of Mathematics, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, TaiwanDepartment of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, TaiwanInstitute of Chemistry, Academia Sinica, Nangang District, Taipei 115, TaiwanDepartment of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, TaiwanDepartment of Applied Mathematics, National Sun Yat-Sen University, Gushan District, Kaohsiung 804, TaiwanDepartment of Obstetrics and Gynecology, Shuang Ho Hospital, Taipei Medical University, Zhonghe District, Taipei 235, TaiwanDepartment of Mathematics, National Taiwan Normal University, Wenshan District, Taipei 106, TaiwanDepartment of Biomedical Sciences, National Chung Cheng University, Min-Hsiung, Chia-Yi 621, TaiwanDepartment of Mathematics, National Tsing Hua University, East District, Hsinchu 300, TaiwanMicroRNAs (miRNAs) play an important role in gene regulation by degradation or translational inhibition of the targeted mRNAs. It has been experimentally shown that the way miRNAs interact with their targets can be used to explain the indirect interactions among their targets, i.e., competing endogenous RNA (ceRNA). However, whether the protein translated from the targeted mRNAs can play any role in this ceRNA network has not been explored. Here we propose a deterministic model to demonstrate that in a network of one miRNA interacting with multiple-targeted mRNAs, the competition between miRNA-targeted mRNAs is not sufficient for the significant change of those targeted mRNA levels, while dramatic changes of these miRNA-targeted mRNAs require transcriptional inhibition of miRNA by its target proteins. When applied to estrogen receptor signaling pathways, the miR-193a targets E2F6 (a target of estrogen receptor), c-KIT (a marker for cancer stemness), and PBX1 (a transcriptional activator for immunosuppressive cytokine, IL-10) in ovarian cancer, such that epigenetic silencing of miR-193a by E2F6 protein is required for the significant change of c-KIT and PBX1 mRNA level for cancer stemness and immunoevasion, respectively, in ovarian cancer carcinogenesishttps://www.mdpi.com/1422-0067/23/4/2277deterministic modelepigeneticsmicroRNAtarget-translated proteinceRNAovarian cancer |
| spellingShingle | Tzy-Wei Huang Frank H. C. Cheng Ching-Cher Sanders Yan Yu-Ming Chuang Chien-Hong Cho Hung-Cheng Lai Shih-Feng Shieh Michael W. Y. Chan Je-Chiang Tsai Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer International Journal of Molecular Sciences deterministic model epigenetics microRNA target-translated protein ceRNA ovarian cancer |
| title | Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer |
| title_full | Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer |
| title_fullStr | Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer |
| title_full_unstemmed | Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer |
| title_short | Interplay between ceRNA and Epigenetic Control of microRNA: Modelling Approaches with Application to the Role of Estrogen in Ovarian Cancer |
| title_sort | interplay between cerna and epigenetic control of microrna modelling approaches with application to the role of estrogen in ovarian cancer |
| topic | deterministic model epigenetics microRNA target-translated protein ceRNA ovarian cancer |
| url | https://www.mdpi.com/1422-0067/23/4/2277 |
| work_keys_str_mv | AT tzyweihuang interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer AT frankhccheng interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer AT chingchersandersyan interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer AT yumingchuang interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer AT chienhongcho interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer AT hungchenglai interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer AT shihfengshieh interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer AT michaelwychan interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer AT jechiangtsai interplaybetweencernaandepigeneticcontrolofmicrornamodellingapproacheswithapplicationtotheroleofestrogeninovariancancer |