Case report: MicroRNA-10b as a therapeutic target in feline metastatic mammary carcinoma and its implications for human clinical trials

Abstract

Ninety percent of deaths from cancer are caused by metastasis. miRNAs are critical players in biological processes such as proliferation, metastasis, apoptosis, and self-renewal. We and others have previously demonstrated that miRNA-10b promotes metastatic cell migration and invasion. Importantly, we also showed that miR-10b is a critical driver of metastatic cell viability and proliferation. To treat established metastases by inhibiting miR-10b, we utilized a therapeutic, termed MN-anti-miR10b, composed of anti-miR-10b antagomirs, conjugated to iron oxide nanoparticles, that serve as delivery vehicles to tumor cells in vivo and a magnetic resonance imaging (MRI) reporter. In our previous studies using murine models of metastatic breast cancer, we demonstrated the effectiveness of MN-anti-miR10b in preventing and eliminating existing metastases. With an outlook toward clinical translation of our therapeutic, here we report studies in large animals (companion cats) with spontaneous feline mammary carcinoma (FMC). We first investigated the expression and tissue localization of miR-10b in feline tumors and metastases and showed remarkable similarity to these features in humans. Next, in the first case study involving this therapeutic we intravenously dosed an FMC patient with MN-anti-miR10b and demonstrated its delivery to the metastatic lesions using MRI. We also showed the initial safety profile of the therapeutic and demonstrated significant change in miR-10b expression and its target HOXD10 after dosing. Our results provide support for using companion animals for further MN-anti-miR10b development as a therapy and serve as a guide for future clinical trials in human patients.

Biomarkers in Breast Cancer: An Old Story with a New End

“…In patients with BC stages I, II, and III, miR-1290 expression was higher than in stage IV patients, which is evidence of it being a potential biomarker for early BC detection [120]. Savan et al [121] showed that miRNA-10b promotes metastatic cell invasion and migration. This study shows that anti-miR10b can inhibit the miR-10b target without toxicity [121].…”

“…Savan et al [121] showed that miRNA-10b promotes metastatic cell invasion and migration. This study shows that anti-miR10b can inhibit the miR-10b target without toxicity [121]. MiR-148a expression was associated with unfavorable clinical parameters and lower survival in BC patients and according to Li et al (2020), MiR-148a plays an oncogenic or tumor suppressor role in different cancer types [122].…”

Assessment of miRNA-10b Expression Levels as a Potential Precursor to Metastasis in Localized and Locally Advanced/Metastatic Breast Cancer among Iraqi Patients

“…By controlling HOXD10, E-cadherin, and syndecan-1, miRNA-10b significantly increases tumor cell invasion and metastasis in the setting of BC [ 11 , 12 ]. Invasion and migration are facilitated by miRNA-10b, an important factor in the metastatic phase of breast cancer [ 13 ]. miR-10b has been described as an oncogenic miRNA that is overexpressed in different types of cancer and is implicated in tumor invasion and metastasis [ 14 ].…”

High expression of miR-107 and miR-17 predicts poor prognosis and guides treatment selection in acute myeloid leukemia

“…MicroRNAs (miRNAs) are regarded as small noncoding RNAs of 20-24 nucleotides that negatively modulate gene expression by directly binding to the 3'-untranslated region (UTR) of target mRNA (3). MiRNAs play vital roles in many physiologic processes, including cell proliferation, differentiation, apoptosis, and self-renewal (4). Aberrant miRNAs are widely involved in cancer biologies, such as tumorigenesis, tumor growth, invasion, metastasis, and angiogenesis (5), and recently, several cancer-associated miRNAs were reported to function as biomarkers to predict the prognosis and treatment response of patients with AML (6)(7)(8).…”