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2017 ; 8
(45
): 78796-78810
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The systemic tumor response to RNase A treatment affects the expression of genes
involved in maintaining cell malignancy
#MMPMID29108266
Mironova N
; Patutina O
; Brenner E
; Kurilshikov A
; Vlassov V
; Zenkova M
Oncotarget
2017[Oct]; 8
(45
): 78796-78810
PMID29108266
show ga
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.
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