Abstract
Background and Objective- The chance of a woman being diagnosed with breast cancer during her lifetime is 1 in 8. The triple negative breast cancer (TNBC) subtype is the most aggressive form of the disease, lacking any targeted treatment and having the highest level of invasiveness resulting in >20% of brain metastasis. The present study continues our quest to characterize the anti-cancer properties of absent peptide nullomer sequences (nulloPs), using an in vivo mice model. To do so, we analyzed the effect of one nulloP (9S1R) on the transcriptome of aggressive mouse TNBC tumors.
Methods- The 4T1.2 luc cells based TNBC mouse model (n=9-10) was used. Treatment group received peptide (100 mg/kg) for a period of 2 weeks, and the untreated group received saline. At termination, tumors (n=3) were excised followed by RNA sequencing. Differential gene expression (DE) analysis was performed using Deseq2 v1.38.1 in R. Fold-changes for each gene were calculated, genes with adjusted p-value < 0.05 were considered DE. String analysis was conducted to identify clustering and specific interactions between the identified genes.
Results- The peptides maintain smaller tumor size, as compared to the control, with reduced luminescence indicative of metabolically inactive tumors. Treatment upregulated 365 genes and downregulated 710 genes when compared to the untreated group. Among upregulated genes Developmental Pathway (13), ECM Organization (12) and Focal Adhesion Related pathways (7) were noteworthy. Downregulated genes were seen in the treated TNBC tumors including Cellular Metabolic Process Related genes (179), specifically (a) mitochondrial genes (40) associated with TCA cycle/oxidative phosphorylation and (b) translation machinery/ribosome assembly genes (45).
Discussion and Conclusions- NulloPs alter tumor transcriptome, rendering them metabolically inactive by downregulating mitochondrial function and ATP production, which corroborates our previous findings.
Methods- The 4T1.2 luc cells based TNBC mouse model (n=9-10) was used. Treatment group received peptide (100 mg/kg) for a period of 2 weeks, and the untreated group received saline. At termination, tumors (n=3) were excised followed by RNA sequencing. Differential gene expression (DE) analysis was performed using Deseq2 v1.38.1 in R. Fold-changes for each gene were calculated, genes with adjusted p-value < 0.05 were considered DE. String analysis was conducted to identify clustering and specific interactions between the identified genes.
Results- The peptides maintain smaller tumor size, as compared to the control, with reduced luminescence indicative of metabolically inactive tumors. Treatment upregulated 365 genes and downregulated 710 genes when compared to the untreated group. Among upregulated genes Developmental Pathway (13), ECM Organization (12) and Focal Adhesion Related pathways (7) were noteworthy. Downregulated genes were seen in the treated TNBC tumors including Cellular Metabolic Process Related genes (179), specifically (a) mitochondrial genes (40) associated with TCA cycle/oxidative phosphorylation and (b) translation machinery/ribosome assembly genes (45).
Discussion and Conclusions- NulloPs alter tumor transcriptome, rendering them metabolically inactive by downregulating mitochondrial function and ATP production, which corroborates our previous findings.
| Original language | American English |
|---|---|
| State | Published - Dec 2022 |
| Event | The 8th Biennial National IDeA Symposium of Biomedical Research Excellence - Duration: 1 Dec 2022 → … |
Conference
| Conference | The 8th Biennial National IDeA Symposium of Biomedical Research Excellence |
|---|---|
| Abbreviated title | NISBRE |
| Period | 1/12/22 → … |
