Ribosomal RNA Transcription Regulation in Breast Cancer

Harold, Cecelia M.; Buhagiar, Amber F.; Yan, CH; Baserga, Susan J.

doi:10.3390/genes12040502

Cited by 25 publications

(25 citation statements)

References 136 publications

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“…3C ). Ribosomal biogenesis is a target for cancer therapy [ 28 ]. A total of 33 ribosome-associated genes were upregulated by DATS treatment ( Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

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Gene Expression Changes by Diallyl Trisulfide Administration in Chemically-induced Mammary Tumors in Rats

Hahm

Singh

2022

J Cancer Prev

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Diallyl trisulfide (DATS) was shown to be a potent inhibitor of luminal-type MCF-7 xenograft growth in vivo. The present study was conducted to determine the preventive effect of DATS administration using an N -methyl- N -nitrosourea (MNU)-induced rat mammary tumor model, which shares molecular resemblance to luminal-type human breast cancers. The DATS administration (50 mg/kg body weight, 5 times/week) was safe, but did not reduce mammary tumor latency, incidence, burden or multiplicity. Therefore, we conducted RNA-seq analysis using mammary tumors from control and DATS-treated rats (n = 3 for each group) to gain insights into lack of mammary tumor prevention by this phytochemical. The gene ontology and the Kyoto encyclopedia of genes and genomes pathway analyses of the RNA-seq data revealed upregulation of genes associated with ribosomes, translation, peptide biosynthetic/metabolic process, and oxidative phosphorylation but downregulation of genes associated with mitogen-activated protein kinases. A total of 33 genes associated with ribosomes were significantly upregulated by DATS treatment, including RPL11 and RPS14 . Western blotting confirmed upregulation of RPL11 and neurofascin protein expression in mammary tumors from DATS-treated rats when compared to controls. A statistically significant increase in protein level of c-Jun N -terminal kinase 2 was also observed in tumors from DATS-treated rats when compared to controls. On the other hand, expression of complex I subunits NDUFV1 or NDUFS1 was not affected by DATS treatment. These results offer potential explanations for ineffectiveness of DATS in the chemically-induced rat mammary tumor model. Inhibitors of the proteins upregulated by DATS may be needed to improve chemopreventive efficacy of this phytochemical.

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“…3C ). Ribosomal biogenesis is a target for cancer therapy [ 28 ]. A total of 33 ribosome-associated genes were upregulated by DATS treatment ( Table S2 ).…”

Section: Resultsmentioning

confidence: 99%

“…The reason for this discrepancy is unclear. Evidence continues to accumulate to implicate ribosomal biogenesis in cancer [ 28 , 32 - 34 ]. As an example, increased ribosomal biogenesis was shown to attenuate the expression and activity of p53 [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

Gene Expression Changes by Diallyl Trisulfide Administration in Chemically-induced Mammary Tumors in Rats

Hahm

Singh

2022

J Cancer Prev

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“…One of the most notable findings in this research is that the ribosome pathway was found to be more frequently associated with the gene regulation of TSGs than non-TSGs in the downregulated genes. Ribosome is a critical cellular component for protein synthesis, and dysregulation of ribosome biogenesis was found to be associated with progression of breast cancer cells [ 43 , 44 , 45 ]. Since the ribosomal RNA or protein modifications affect cancer development [ 46 , 47 ], it is possible that differential regulations of ribosomal genes might influence cancer cell development via TSGs.…”

Section: Discussionmentioning

confidence: 99%

Uncovering Oncogenic Mechanisms of Tumor Suppressor Genes in Breast Cancer Multi-Omics Data

Cho

2022

IJMS

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Tumor suppressor genes (TSGs) are essential genes in the development of cancer. While they have many roles in normal cells, mutation and dysregulation of the TSGs result in aberrant molecular processes in cancer cells. Therefore, understanding TSGs and their roles in the oncogenic process is crucial for prevention and treatment of cancer. In this research, multi-omics breast cancer data were used to identify molecular mechanisms of TSGs in breast cancer. Differentially expressed genes and differentially coexpressed genes were identified in four large-scale transcriptomics data from public repositories and multi-omics data analyses of copy number, methylation and gene expression were performed. The results of the analyses were integrated using enrichment analysis and meta-analysis of a p-value summation method. The integrative analysis revealed that TSGs have a significant relationship with genes of gene ontology terms that are related to cell cycle, genome stability, RNA processing and metastasis, indicating the regulatory mechanisms of TSGs on cancer cells. The analysis frame and research results will provide valuable information for the further identification of TSGs in different types of cancers.

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“…Inhibitors of topoisomerase I activity, specifically camptothecin, irinotecan, and topotecian can also efficiently disrupt pol I transcription [ 134 , 135 ]. Now the rDNA and its functions are becoming a specific target of the anti-cancer therapy [ 136 ]. The first of the designed drugs is CX-3543 (quarfloxin), it specifically inhibits the elongation stage of pol I transcription by preventing the stabilizing interactions between nucleolin and G-quadruplexes in the rDNA gene.…”

Section: Ribosomal Dna and Cancer Therapymentioning

confidence: 99%

Human rDNA and Cancer

Smirnov

Chmúrčiaková

Cmarko

2021

Cells

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In human cells, each rDNA unit consists of the ~13 kb long ribosomal part and ~30 kb long intergenic spacer (IGS). The ribosomal part, transcribed by RNA polymerase I (pol I), includes genes coding for 18S, 5.8S, and 28S RNAs of the ribosomal particles, as well as their four transcribed spacers. Being highly repetitive, intensively transcribed, and abundantly methylated, rDNA is a very fragile site of the genome, with high risk of instability leading to cancer. Multiple small mutations, considerable expansion or contraction of the rDNA locus, and abnormally enhanced pol I transcription are usual symptoms of transformation. Recently it was found that both IGS and the ribosomal part of the locus contain many functional/potentially functional regions producing non-coding RNAs, which participate in the pol I activity regulation, stress reactions, and development of the malignant phenotype. Thus, there are solid reasons to believe that rDNA locus plays crucial role in carcinogenesis. In this review we discuss the data concerning the human rDNA and its closely associated factors as both targets and drivers of the pathways essential for carcinogenesis. We also examine whether variability in the structure of the locus may be blamed for the malignant transformation. Additionally, we consider the prospects of therapy focused on the activity of rDNA.

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Ribosomal RNA Transcription Regulation in Breast Cancer

Cited by 25 publications

References 136 publications

Gene Expression Changes by Diallyl Trisulfide Administration in Chemically-induced Mammary Tumors in Rats

Gene Expression Changes by Diallyl Trisulfide Administration in Chemically-induced Mammary Tumors in Rats

Uncovering Oncogenic Mechanisms of Tumor Suppressor Genes in Breast Cancer Multi-Omics Data

Human rDNA and Cancer

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