Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels
Rlip76 (Rlip) is a multifunctional membrane protein that facilitates the high metabolic rates of cancer cells through the efflux of toxic metabolites and other functions. Rlip inhibition or depletion results in broad-spectrum anti-cancer effects in vitro and in vivo. Rlip depletion effectively suppr...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/3/527 |
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| author | Ashly Hindle Chhanda Bose Jihyun Lee Philip T. Palade Christopher J. Peterson P. Hemachandra Reddy Sanjay Awasthi Sharda P. Singh |
| author_facet | Ashly Hindle Chhanda Bose Jihyun Lee Philip T. Palade Christopher J. Peterson P. Hemachandra Reddy Sanjay Awasthi Sharda P. Singh |
| author_sort | Ashly Hindle |
| collection | DOAJ |
| description | Rlip76 (Rlip) is a multifunctional membrane protein that facilitates the high metabolic rates of cancer cells through the efflux of toxic metabolites and other functions. Rlip inhibition or depletion results in broad-spectrum anti-cancer effects in vitro and in vivo. Rlip depletion effectively suppresses malignancy and causes global reversion of characteristic CpG island methylomic and transcriptomic aberrations in the p53-null mouse model of spontaneous carcinogenesis through incompletely defined signaling and transcriptomic mechanisms. The methylome and transcriptome are normally regulated by the concerted actions of several mechanisms that include chromatin remodeling, promoter methylation, transcription factor interactions, and miRNAs. The present studies investigated the interaction of Rlip depletion or inhibition with the promoter methylation and transcription of selected cancer-related genes identified as being affected by Rlip depletion in our previous studies. We constructed novel promoter CpG island/luciferase reporter plasmids that respond only to CpG methylation and transcription factors. We found that Rlip depletion regulated expression by a transcription factor-based mechanism that functioned independently of promoter CpG methylation, lipid peroxidation, and p53 status. |
| first_indexed | 2024-03-10T00:07:52Z |
| format | Article |
| id | doaj.art-1eb2711b3bd64df9a2a6065e5041301c |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T00:07:52Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-1eb2711b3bd64df9a2a6065e5041301c2023-11-23T16:04:20ZengMDPI AGCancers2072-66942022-01-0114352710.3390/cancers14030527Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory LevelsAshly Hindle0Chhanda Bose1Jihyun Lee2Philip T. Palade3Christopher J. Peterson4P. Hemachandra Reddy5Sanjay Awasthi6Sharda P. Singh7Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USADepartment of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USARlip76 (Rlip) is a multifunctional membrane protein that facilitates the high metabolic rates of cancer cells through the efflux of toxic metabolites and other functions. Rlip inhibition or depletion results in broad-spectrum anti-cancer effects in vitro and in vivo. Rlip depletion effectively suppresses malignancy and causes global reversion of characteristic CpG island methylomic and transcriptomic aberrations in the p53-null mouse model of spontaneous carcinogenesis through incompletely defined signaling and transcriptomic mechanisms. The methylome and transcriptome are normally regulated by the concerted actions of several mechanisms that include chromatin remodeling, promoter methylation, transcription factor interactions, and miRNAs. The present studies investigated the interaction of Rlip depletion or inhibition with the promoter methylation and transcription of selected cancer-related genes identified as being affected by Rlip depletion in our previous studies. We constructed novel promoter CpG island/luciferase reporter plasmids that respond only to CpG methylation and transcription factors. We found that Rlip depletion regulated expression by a transcription factor-based mechanism that functioned independently of promoter CpG methylation, lipid peroxidation, and p53 status.https://www.mdpi.com/2072-6694/14/3/527RALBP1Rlipmethylationtranscriptionregulationbreast cancer |
| spellingShingle | Ashly Hindle Chhanda Bose Jihyun Lee Philip T. Palade Christopher J. Peterson P. Hemachandra Reddy Sanjay Awasthi Sharda P. Singh Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels Cancers RALBP1 Rlip methylation transcription regulation breast cancer |
| title | Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels |
| title_full | Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels |
| title_fullStr | Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels |
| title_full_unstemmed | Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels |
| title_short | Rlip Depletion Alters Oncogene Transcription at Multiple Distinct Regulatory Levels |
| title_sort | rlip depletion alters oncogene transcription at multiple distinct regulatory levels |
| topic | RALBP1 Rlip methylation transcription regulation breast cancer |
| url | https://www.mdpi.com/2072-6694/14/3/527 |
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