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Abstract

Heightened co-expression and dysregulated signaling associated with Tolllike receptor 3 (TLR3) and Wnt5a is an integral component of solid tumors and hematological malignancies. Our previous findings in pancreatic cancer and melanoma suggest that inhibition of these pathways by a TLR3 signaling inhibitor, phenylmethimazole (C10), results in significantly decreased IL-6 levels, STAT3 phosphorylation, minimal cancer cell migration and reduced cancer cell growth in vitro and in vivo. In this study, we extended our earlier observations by performing studies in human breast cancer cells. We found that human MCF-7 breast cancer cells express high basal levels of TLR3 and Wnt5a RNA. C10 treatment resulted in significantly decreased TLR3 and Wnt5a expression levels. This functionally translated into significantly reduced IL-6 levels and STAT3 phosphorylation in vitro. In addition, the inhibition of this signaling cascade by C10 further resulted in decreased cell viability and migration of MCF-7 cells. Strikingly, the combination of C10 and tamoxifen, the standard of care therapy for breast cancer, further decrease cancer cell growth better than either agent alone. These data support the novel finding that inhibition of TLR3 signaling in combination with tamoxifen, may increase the effectiveness of current treatments of breast cancer.

<p>MicroRNA-769-5p Inhibits Pancreatic Ductal Adenocarcinoma Progression by Directly Targeting and Downregulating ETS Proto-Oncogene 1</p>

“…MiR-769 is downregulated in non-small cell lung cancer, and this downregulation is significantly associated with the clinical stage and lymph node metastasis. 26 Patients with non-small cell lung cancer harboring low miR-769 levels show poorer clinical outcomes than do patients with high miR-769 levels. 26 In contrast, miR-769 is upregulated in melanoma.…”

“…26 Patients with non-small cell lung cancer harboring low miR-769 levels show poorer clinical outcomes than do patients with high miR-769 levels. 26 In contrast, miR-769 is upregulated in melanoma. 27 These conflicting findings indicate that the human miR-769 expression pattern is cancer-specific.…”

“…MiR-769 directly targets TGFBR1 mRNA to inhibit the growth and metastasis of non-small cell lung cancer cells both in vitro and in vivo. 26 By contrast, miR-769 is identified as an oncogenic miRNA in melanoma. Upregulation of miR-769 promotes melanoma cell growth and colony formation in vitro by directly targeting GSK3B mRNA.…”

“…PDAC is yet to be elucidated. MiR-769-5p (miR-769) has attracted our attention owing to its significant participation in the regulation of cancer biology of non-small cell lung cancer 26 and melanoma. 27 Nonetheless, the expression pattern, biological function, and the mechanisms of action of miR-769 in PDAC are yet to be fully elucidated.…”

<p>MicroRNA-769-5p Promotes The Growth Of Glioma Cells By Targeting Lysine Methyltransferase 2A</p>

“…miR-769-5p expression is frequently reduced in colorectal cancer (CRC), and suppresses cell proliferation and invasion by inhibiting cyclin-dependent kinase 1 (CDK1) and hes related family bHLH transcription factor with YRPW motif 1 (HEY1) 18,19. Moreover, miR-769-5p suppressed the proliferation, migration and invasion of NSCLC cells by inhibiting transforming growth factor beta receptor 1 (TGFBR1) 20. Additionally, long noncoding RNA (lncRNA) LINC00460 functions as a molecular sponge for miR-769-5p to promote epidermal growth factor receptor (EGFR) and accordingly exerts an oncogenic role in NSCLC 21.…”