APE 1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNA sequencing
Article Swipe
Fenil Shah
,
Emery Goossens
,
Nadia A. Lanman
,
Michelle Grimard
,
Mark R. Kelley
,
Melissa L. Fishel
·
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1002/1878-0261.12138
YOU?
·
· 2017
· Open Access
·
· DOI: https://doi.org/10.1002/1878-0261.12138
Apurinic/apyrimidinic endonuclease 1/redox factor‐1 ( APE 1/Ref‐1 or APE 1) is a multifunctional protein that regulates numerous transcription factors associated with cancer‐related pathways. Because APE 1 is essential for cell viability, generation of APE 1‐knockout cell lines and determining a comprehensive list of genes regulated by APE 1 has not been possible. To circumvent this challenge, we utilized single‐cell RNA sequencing to identify differentially expressed genes (DEGs) in relation to APE 1 protein levels within the cell. Using a straightforward yet novel statistical design, we identified 2837 genes whose expression is significantly changed following APE 1 knockdown. Using this gene expression profile, we identified multiple new pathways not previously linked to APE 1, including the EIF 2 signaling and mechanistic target of Rapamycin pathways and a number of mitochondrial‐related pathways. We demonstrate that APE 1 has an effect on modifying gene expression up to a threshold of APE 1 expression, demonstrating that it is not necessary to completely knockout APE 1 in cells to accurately study APE 1 function. We validated the findings using a selection of the DEGs along with si RNA knockdown and qRT ‐ PCR . Testing additional patient‐derived pancreatic cancer cells reveals particular genes ( ITGA 1 , TNFAIP 2 , COMMD 7 , RAB 3D ) that respond to APE 1 knockdown similarly across all the cell lines. Furthermore, we verified that the redox function of APE 1 was responsible for driving gene expression of mitochondrial genes such as PRDX 5 and genes that are important for proliferation such as SIPA 1 and RAB 3D by treating with APE 1 redox‐specific inhibitor, APX 3330. Our study identifies several novel genes and pathways affected by APE 1, as well as tumor subtype specificity. These findings will allow for hypothesis‐driven approaches to generate combination therapies using, for example, APE 1 inhibitor APX 3330 with other approved FDA drugs in an innovative manner for pancreatic and other cancer treatments.
Related Topics
Concepts
Gene knockdown
Gene expression
Pancreatic ductal adenocarcinoma
RNA
Molecular biology
Gene
Biology
Cell
Cell biology
Chemistry
Computational biology
Genetics
Pancreatic cancer
Cancer
Metadata
- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1002/1878-0261.12138
- https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.12138
- OA Status
- gold
- Cited By
- 38
- References
- 99
- Related Works
- 10
- OpenAlex ID
- https://openalex.org/W2754623901
All OpenAlex metadata
Raw OpenAlex JSON
- OpenAlex ID
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https://openalex.org/W2754623901Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1002/1878-0261.12138Digital Object Identifier
- Title
-
APE 1/Ref‐1 knockdown in pancreatic ductal adenocarcinoma – characterizing gene expression changes and identifying novel pathways using single‐cellRNA sequencingWork title - Type
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articleOpenAlex work type
- Language
-
enPrimary language
- Publication year
-
2017Year of publication
- Publication date
-
2017-09-18Full publication date if available
- Authors
-
Fenil Shah, Emery Goossens, Nadia A. Lanman, Michelle Grimard, Mark R. Kelley, Melissa L. FishelList of authors in order
- Landing page
-
https://doi.org/10.1002/1878-0261.12138Publisher landing page
- PDF URL
-
https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.12138Direct link to full text PDF
- Open access
-
YesWhether a free full text is available
- OA status
-
goldOpen access status per OpenAlex
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https://febs.onlinelibrary.wiley.com/doi/pdfdirect/10.1002/1878-0261.12138Direct OA link when available
- Concepts
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Gene knockdown, Gene expression, Pancreatic ductal adenocarcinoma, RNA, Molecular biology, Gene, Biology, Cell, Cell biology, Chemistry, Computational biology, Genetics, Pancreatic cancer, CancerTop concepts (fields/topics) attached by OpenAlex
- Cited by
-
38Total citation count in OpenAlex
- Citations by year (recent)
-
2025: 6, 2024: 2, 2023: 4, 2022: 1, 2021: 6Per-year citation counts (last 5 years)
- References (count)
-
99Number of works referenced by this work
- Related works (count)
-
10Other works algorithmically related by OpenAlex
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| corresponding_author_ids | https://openalex.org/A5055500811 |
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| institutions_distinct_count | 6 |
| corresponding_institution_ids | https://openalex.org/I4394709130, https://openalex.org/I55769427 |
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