PIK3CA Cooperates with KRAS to Promote MYC Activity and Tumorigenesis via the Bromodomain Protein BRD9
Abstract
:1. Introduction
2. Results
2.1. Contribution of Oncogenic PIK3CA and KRAS to Anchorage-Independent Growth, Proliferation and Migration
2.2. KRAS and PIK3CA Oncogenes Cooperate to Generate a Transcriptional Signature Enriched for EMT, Cell Cycle and MYC Target Genes
2.3. Oncogenic PIK3CA and KRAS Induce the Expression of the Bromodomain-Containing Protein BRD9
2.4. BRD9 is Part of the SWI-SNF Complex and Augments MYC Activity
2.5. BRD9 Inhibition Blocks MYC Expression and MYC Inhibition Blocks Anchorage-Independent Growth
3. Discussion
4. Materials and Methods
4.1. Cell Culture and Viability Assays
4.2. Next-Generation Sequencing
4.3. Gene Expression Analysis
4.4. Plasmids and CRISPR-Cas9 Gene Editing
4.5. RT-qPCR
4.6. Immunoblotting
4.7. Immunoprecipitation
4.8. Chromatin Immunoprecipitation
4.9. Colony Formation in Semisolid Medium
4.10. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Rank | DKI vs. WT | log2FC | DKI vs. PIK3CAH1047R | log2FC | DKI vs. KRASG12V | log2FC |
---|---|---|---|---|---|---|
1 | COL4A1 | 4.19 | DHRS3 | 5.40 | CLPTM1L | 1.08 |
2 | TFPI2 | 4.09 | TFPI2 | 4.29 | CCT5 | 1.14 |
3 | FAM110C | 4.47 | TGFBI | 4.14 | MRPS30 | 1.06 |
4 | ARL4C | 3.84 | TINAGL1 | 4.04 | NSUN2 | 1.01 |
5 | TCF19 | 3.73 | COL4A1 | 3.97 | LPCAT1 | 1.06 |
6 | DHRS3 | 5.33 | FAM110C | 3.78 | BASP1 | 0.98 |
7 | TINAGL1 | 4.18 | TCF19 | 3.73 | PEAR1 | 2.18 |
8 | LMNB2 | 3.43 | LMNB2 | 3.67 | BRD9 | 1.07 |
9 | PROSER2 | 3.42 | MYBL2 | 3.59 | VIM | 1.22 |
10 | ADAM19 | 4.66 | CCT2 | 3.54 | ANKH | 1.16 |
11 | PHLDA1 | 3.40 | ADAM19 | 3.49 | TRIP13 | 1.05 |
12 | TGFBI | 4.23 | UBA2 | 3.44 | IRX4 | 1.17 |
13 | CCT2 | 2.80 | SRP14 | 3.38 | OTULIN | 0.83 |
14 | TXNRD1 | 2.91 | EIF1 | 3.18 | ICE1 | 0.94 |
15 | UBA2 | 3.25 | MCM2 | 3.17 | TARS | 0.93 |
16 | TRIP13 | 3.44 | RPL7 | 3.10 | DNAJC21 | 1.03 |
17 | LTBP1 | 3.06 | NSUN2 | 3.09 | LMBRD2 | 1.06 |
18 | NSUN2 | 3.04 | CSTA | 2.99 | ZNF622 | 0.93 |
19 | MCM2 | 3.61 | GLRX | 2.93 | CEP72 | 1.26 |
20 | UHRF1 | 3.52 | RPS7 | 2.86 | KCNK6 | 1.03 |
DKI vs. WT | DKI vs. PIK3CA_H1047R | DKI vs. KRAS_G12V |
---|---|---|
EPITHELIAL_MESENCHYMAL_TRANSITION | E2F_TARGETS | MYC_TARGETS_V1 |
E2F_TARGETS | G2M_CHECKPOINT | E2F_TARGETS |
G2M_CHECKPOINT | EPITHELIAL_MESENCHYMAL_TRANSITION | OXIDATIVE_PHOSPHORYLATION |
KRAS_SIGNALING_UP | KRAS_SIGNALING_UP | G2M_CHECKPOINT |
APICAL_JUNCTION | MITOTIC_SPINDLE | MYC_TARGETS_V2 |
TNFA_SIGNALING_VIA_NFKB | ESTROGEN_RESPONSE | MTORC1_SIGNALING |
MTORC1_SIGNALING | APICAL_JUNCTION | APOPTOSIS |
TGF_BETA_SIGNALING | MTORC1_SIGNALING | UNFOLDED_PROTEIN_RESPONSE |
WNT_BETA_CATENIN_SIGNALING | MYC_TARGETS_V1 | |
IL2_STAT5_SIGNALING | TNFA_SIGNALING_VIA_NFKB |
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Bell, C.M.; Raffeiner, P.; Hart, J.R.; Vogt, P.K. PIK3CA Cooperates with KRAS to Promote MYC Activity and Tumorigenesis via the Bromodomain Protein BRD9. Cancers 2019, 11, 1634. https://doi.org/10.3390/cancers11111634
Bell CM, Raffeiner P, Hart JR, Vogt PK. PIK3CA Cooperates with KRAS to Promote MYC Activity and Tumorigenesis via the Bromodomain Protein BRD9. Cancers. 2019; 11(11):1634. https://doi.org/10.3390/cancers11111634
Chicago/Turabian StyleBell, Catherine M., Philipp Raffeiner, Jonathan R. Hart, and Peter K. Vogt. 2019. "PIK3CA Cooperates with KRAS to Promote MYC Activity and Tumorigenesis via the Bromodomain Protein BRD9" Cancers 11, no. 11: 1634. https://doi.org/10.3390/cancers11111634