Oncotarget

Research Papers:

The systemic tumor response to RNase A treatment affects the expression of genes involved in maintaining cell malignancy

Nadezhda Mironova, Olga Patutina, Evgenyi Brenner, Alexander Kurilshikov, Valentin Vlassov and Marina Zenkova _

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2017; 8:78796-78810. https://doi.org/10.18632/oncotarget.20228

Metrics: PDF 1142 views  |   HTML 1986 views  |   ?  


Abstract

Nadezhda Mironova1, Olga Patutina1, Evgenyi Brenner1, Alexander Kurilshikov1,2, Valentin Vlassov1 and Marina Zenkova1

1Institute of Chemical Biology and Fundamental Medicine SB RAS, Novosibirsk, Russia

2Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands

Correspondence to:

Marina Zenkova, email: marzen@niboch.nsc.ru

Nadezhda Mironova, email: mironova@niboch.nsc.ru

Keywords: antitumor ribonucleases, RNase A, sequencing, metabolism of cancer cells, cancer-related pathways

Received: May 19, 2017   Accepted: July 25, 2017   Published: August 12, 2017

ABSTRACT

Recently, pancreatic RNase A was shown to inhibit tumor and metastasis growth that accompanied by global alteration of miRNA profiles in the blood and tumor tissue (Mironova et al., 2013). Here, we performed a whole transcriptome analysis of murine Lewis lung carcinoma (LLC) after treatment of tumor-bearing mice with RNase A. We identified 966 differentially expressed transcripts in LLC tumors, of which 322 were upregulated and 644 were downregulated after RNase A treatment. Many of these genes are involved in signaling pathways that regulate energy metabolism, cell-growth promoting and transforming activity, modulation of the cancer microenvironment and extracellular matrix components, and cellular proliferation and differentiation. Following RNase A treatment, we detected an upregulation of carbohydrate metabolism, inositol phosphate cascade and oxidative phosphorylation, re-arrangement of cell adhesion, cell cycle control, apoptosis, and transcription. Whereas cancer-related signaling pathways (e.g., TGF-beta, JAK/STAT, and Wnt) were downregulated following RNase A treatment, as in the case of the PI3K/AKT pathway, which is involved in the progression of non-small lung cancer. RNase A therapy resulted in the downregulation of genes that inhibit the biogenesis of some miRNAs, particularly the let-7 miRNA family.

Taken together, our data suggest that the antitumor activity and decreased invasion potential of tumor cells caused by RNase A are associated with enhanced energy cascade functioning, rearrangement of cancer-related events regulating cell growth and dissemination, and attenuation of signaling pathways having tumor-promoting activity. Thus, RNase A can be proposed as a potential component of anticancer therapy with multiple modes of action.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 20228