Abstract
The important role of miRNA in cell proliferation and differentiation has raised interest in exogenous ribonucleases (RNases) as tools to control tumour-associated intracellular and extracellular miRNAs. In this work, we evaluated the effects of the RNase binase from Bacillus pumilus on small non-coding regulatory RNAs in the context of mouse RLS40 lymphosarcoma inhibition. In vitro binase exhibited cytotoxicity towards RLS40 cells via apoptosis induction through caspase-3/caspase-7 activation and decreased the levels of miR-21a, let-7g, miR-31 and miR-155. Intraperitoneal injections of binase in RLS40-bearing mice resulted in the retardation of primary tumour growth by up to 60% and inhibition of metastasis in the liver by up to 86%, with a decrease in reactive inflammatory infiltration and mitosis in tumour tissue. In the blood serum of binase-treated mice, decreases in the levels of most studied miRNAs were observed, excluding let-7g, while in tumour tissue, the levels of oncomirs miR-21, miR-10b, miR-31 and miR-155, and the oncosuppressor let-7g, were upregulated. Analysis of binase-susceptible miRNAs and their regulatory networks showed that the main modulated events were transcription and translation control, the cell cycle, cell proliferation, adhesion and invasion, apoptosis and autophagy, as well as some other tumour-related cascades, with an impact on the observed antitumour effects.
Highlights
The microRNAs discovered in animals and plants [1] are non-coding RNAs with a length of 19–25 nucleotides [2,3] that regulate gene expression at the post-transcriptional level via specific complementary sites of target mRNAs, causing translational repression or degradation [4]. miRNAs have been found to be significant modulators of a variety of cellular processes [5], including angiogenesis [6], apoptosis [7], the cell cycle [8], proliferation [9] and telomerase activity [10]
The first study of the ability of binase to retard primary tumour growth and metastasis development was performed using three tumour models of different histological types with strong relevance to human tumours: Lewis lung carcinoma (LLC) with an epithelial origin is related to human non-small cell lung cancer [44]; mouse RLS40 lymphosarcoma is derived from hematopoietic tissue and displays a multidrug resistance phenotype related to human diffuse large B-cell lymphoma; melanoma B-16 arose from neuroectodermal tissue and is related to human metastatic melanoma [45]
Previous data showed that intraperitoneal injections of binase resulted in the retardation of primary tumour growth by up to 45% in the LLC and RLS40 models and inhibited metastasis development by up to 50% in the case of LLC and RLS40 and up to 70% in B16 melanoma [28]
Summary
The microRNAs (miRNAs) discovered in animals and plants [1] are non-coding RNAs with a length of 19–25 nucleotides [2,3] that regulate gene expression at the post-transcriptional level via specific complementary sites of target mRNAs, causing translational repression or degradation [4]. miRNAs have been found to be significant modulators of a variety of cellular processes [5], including angiogenesis [6], apoptosis [7], the cell cycle [8], proliferation [9] and telomerase activity [10]. MiRNAs have been found to be significant modulators of a variety of cellular processes [5], including angiogenesis [6], apoptosis [7], the cell cycle [8], proliferation [9] and telomerase activity [10]. They are thought to play a key role in disease development, in oncological diseases [11]. These findings direct attention to exogenous RNases as tools to compensate for the malfunction of endogenous ones
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
