Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs
As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Phelps et al., 2016) that described how we intended to replicate selected experiments from the paper ‘Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs’ (Tay et al., 2011)...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-10-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/56651 |
| _version_ | 1818024051606552576 |
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| author | Hongyan Wang Hanna S Radomska Mitch A Phelps Reproducibility Project: Cancer Biology |
| author_facet | Hongyan Wang Hanna S Radomska Mitch A Phelps Reproducibility Project: Cancer Biology |
| author_sort | Hongyan Wang |
| collection | DOAJ |
| description | As part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Phelps et al., 2016) that described how we intended to replicate selected experiments from the paper ‘Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs’ (Tay et al., 2011). Here, we report the results. We found depletion of putative PTEN competing endogenous mRNAs (ceRNAs) in DU145 cells did not impact PTEN 3’UTR regulation using a reporter, while the original study reported decreased activity when SERINC1, VAPA, and CNOT6L were depleted (Figure 3C; Tay et al., 2011). Using the same reporter, we found decreased activity when ceRNA 3’UTRs were overexpressed, while the original study reported increased activity (Figure 3D; Tay et al., 2011). In HCT116 cells, ceRNA depletion resulted in decreased PTEN protein levels, a result similar to the findings reported in the original study (Figure 3G,H; Tay et al., 2011); however, while the original study reported an attenuated ceRNA effect in microRNA deficient (DicerEx5) HCT116 cells, we observed increased PTEN protein levels. Further, we found depletion of the ceRNAs VAPA or CNOT6L did not statistically impact DU145, wild-type HCT116, or DicerEx5 HCT116 cell proliferation. The original study reported increased DU145 and wild-type HCT116 cell proliferation when these ceRNAs were depleted, which was attenuated in the DicerEx5 HCT116 cells (Figure 5B; Tay et al., 2011). Differences between the original study and this replication attempt, such as variance between biological repeats, are factors that might have influenced the results. Finally, we report meta-analyses for each result. |
| first_indexed | 2024-12-10T03:54:04Z |
| format | Article |
| id | doaj.art-7bb39d2314aa4e278343bdfa8284687f |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T03:54:04Z |
| publishDate | 2020-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-7bb39d2314aa4e278343bdfa8284687f2022-12-22T02:03:11ZengeLife Sciences Publications LtdeLife2050-084X2020-10-01910.7554/eLife.56651Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAsHongyan Wang0Hanna S Radomska1Mitch A Phelps2Reproducibility Project: Cancer Biology3Pharmacoanalytic Shared Resource (PhASR), Comprehensive Cancer Center, The Ohio State University, Columbus, United StatesPharmacoanalytic Shared Resource (PhASR), Comprehensive Cancer Center, The Ohio State University, Columbus, United StatesPharmacoanalytic Shared Resource (PhASR), Comprehensive Cancer Center, The Ohio State University, Columbus, United StatesScience Exchange, Palo Alto, United States; Center for Open Science, Charlottesville, United StatesAs part of the Reproducibility Project: Cancer Biology, we published a Registered Report (Phelps et al., 2016) that described how we intended to replicate selected experiments from the paper ‘Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs’ (Tay et al., 2011). Here, we report the results. We found depletion of putative PTEN competing endogenous mRNAs (ceRNAs) in DU145 cells did not impact PTEN 3’UTR regulation using a reporter, while the original study reported decreased activity when SERINC1, VAPA, and CNOT6L were depleted (Figure 3C; Tay et al., 2011). Using the same reporter, we found decreased activity when ceRNA 3’UTRs were overexpressed, while the original study reported increased activity (Figure 3D; Tay et al., 2011). In HCT116 cells, ceRNA depletion resulted in decreased PTEN protein levels, a result similar to the findings reported in the original study (Figure 3G,H; Tay et al., 2011); however, while the original study reported an attenuated ceRNA effect in microRNA deficient (DicerEx5) HCT116 cells, we observed increased PTEN protein levels. Further, we found depletion of the ceRNAs VAPA or CNOT6L did not statistically impact DU145, wild-type HCT116, or DicerEx5 HCT116 cell proliferation. The original study reported increased DU145 and wild-type HCT116 cell proliferation when these ceRNAs were depleted, which was attenuated in the DicerEx5 HCT116 cells (Figure 5B; Tay et al., 2011). Differences between the original study and this replication attempt, such as variance between biological repeats, are factors that might have influenced the results. Finally, we report meta-analyses for each result.https://elifesciences.org/articles/56651reproducibilityreplicationmetasciencePTENceRNAmicroRNA |
| spellingShingle | Hongyan Wang Hanna S Radomska Mitch A Phelps Reproducibility Project: Cancer Biology Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs eLife reproducibility replication metascience PTEN ceRNA microRNA |
| title | Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs |
| title_full | Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs |
| title_fullStr | Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs |
| title_full_unstemmed | Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs |
| title_short | Replication Study: Coding-independent regulation of the tumor suppressor PTEN by competing endogenous mRNAs |
| title_sort | replication study coding independent regulation of the tumor suppressor pten by competing endogenous mrnas |
| topic | reproducibility replication metascience PTEN ceRNA microRNA |
| url | https://elifesciences.org/articles/56651 |
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