Involvement of Differentially Expressed microRNAs in the PEGylated Liposome Encapsulated 188Rhenium-Mediated Suppression of Orthotopic Hypopharyngeal Tumor

Abstract

Hypopharyngeal cancer (HPC) accounts for the lowest survival rate among all types of head and neck cancers (HNSCC). However, the therapeutic approach for HPC still needs to be investigated. In this study, a theranostic 188Re-liposome was prepared to treat orthotopic HPC tumors and analyze the deregulated microRNA expressive profiles. The therapeutic efficacy of 188Re-liposome on HPC tumors was evaluated using bioluminescent imaging followed by next generation sequencing (NGS) analysis, in order to address the deregulated microRNAs and associated signaling pathways. The differentially expressed microRNAs were also confirmed using clinical HNSCC samples and clinical information from The Cancer Genome Atlas (TCGA) database. Repeated doses of 188Re-liposome were administrated to tumor-bearing mice, and the tumor growth was apparently suppressed after treatment. For NGS analysis, 13 and 9 microRNAs were respectively up-regulated and down-regulated when the cutoffs of fold change were set to 5. Additionally, miR-206-3p and miR-142-5p represented the highest fold of up-regulation and down-regulation by 188Re-liposome, respectively. According to Differentially Expressed MiRNAs in human Cancers (dbDEMC) analysis, most of 188Re-liposome up-regulated microRNAs were categorized as tumor suppressors, while down-regulated microRNAs were oncogenic. The KEGG pathway analysis showed that cancer-related pathways and olfactory and taste transduction accounted for the top pathways affected by 188Re-liposome. 188Re-liposome down-regulated microRNAs, including miR-143, miR-6723, miR-944, and miR-136 were associated with lower survival rates at a high expressive level. 188Re-liposome could suppress the HPC tumors in vivo, and the therapeutic efficacy was associated with the deregulation of microRNAs that could be considered as a prognostic factor.

Brachytherapy Approach Using 177Lu Conjugated Gold Nanostars and Evaluation of Biodistribution, Tumor Retention, Dosimetry and Therapeutic Efficacy in Head and Neck Tumor Model

“…We have previously shown that intravenous injection of 188 Re-liposome radiopharmaceutical could induce let-7i microRNA in orthotopic HNSCC tumors [29]. Furthermore, RNA-seq analysis revealed that a panel of microRNAs with tumor-suppressive and oncogenic characteristics were up-regulated and down-regulated, respectively, in 188 Re-liposome treated HNSCC tumors [38]. The expression of EMT molecules was also influenced by 188 Re-liposome to account for the potential therapeutic efficacy of this radiopharmaceutical [7].…”

LINC01816 promotes the migration, invasion and epithelial‑mesenchymal transition of thyroid carcinoma cells by sponging miR‑34c‑5p and regulating CRABP2 expression levels

“…Wang et al determined that miR-34c-5p targeted flotillin 2 to inhibit the proliferation, migration and invasion of osteosarcoma cells, downregulate the protein expression levels of cyclin D1, matrix metalloproteinase (MMP)-2 and MMP-9, and upregulate the protein expression levels of p21 (51). The signaling pathways associated with miR-34c-5p target genes are known to be closely associated with tumor processes (23)(24)(25). The results of the present study also revealed that E-cadherin expression levels were significantly downregulated following the inhibition of miR-34c-5p.…”

“…Shen et al indicated that the lncRNA KCNQ1 opposite strand/antisense transcript 1 sponged miR-34c-5p to promote osteosarcoma growth via aldolase, fructose-bisphosphate A-enhanced aerobic glycolysis (22). Numerous other studies have revealed that miR-34c-5p was closely related to the development of numerous types of human malignant cancer (23)(24)(25).…”

Translating Research for the Radiotheranostics of Nanotargeted 188Re-Liposome

“…Microarray array analysis revealed the tumor suppressor microRNA let-7 could be induced by 188 Re-liposome to regulate downstream genes in human head and neck squamous cell carcinoma (HNSCC) [ 27 ]. Most 188 Re-liposome that up-regulate microRNAs, including miR-206-3p, were categorized as tumor suppressors, while down-regulate microRNAs, including miR-142-5P, were oncogenic [ 28 ]. Studies on the regulation of microRNAs correlate to the therapeutic efficacy of 188 Re-liposome in HNSCC tumor [ 27 , 28 ].…”

“…Most 188 Re-liposome that up-regulate microRNAs, including miR-206-3p, were categorized as tumor suppressors, while down-regulate microRNAs, including miR-142-5P, were oncogenic [ 28 ]. Studies on the regulation of microRNAs correlate to the therapeutic efficacy of 188 Re-liposome in HNSCC tumor [ 27 , 28 ]. The evidence indicated 188 Re-liposome enhances various anti-tumor mechanisms in tumor therapy.…”