Modulation of the dual‐faced effects of miR‐141 with chitosan/miR‐141 nanoplexes in breast cancer cells

Abstract

Background miR‐141, known as a tumor suppressive microRNA, is downregulated in breast cancer. However, recent contrasting studies report that it also acts as oncogene when it is upregulated. The present study aimed to investigate whether miR‐141 is a tumor suppressor or oncogenic when it reaches normal levels in chitosan/miR‐141 nanoplexes. Methods Chitosan nanoplexes were prepared using simple complexation method. Nanoplexes were characterized by a gel retardation assay and zeta potential and particle size measurements. To determine the expression level of miR‐141, a quantitative real‐time polymerase chain reaction was performed. The effects of miR‐141 mimics were investigated with respect to angiogenesis by vascular endothelial growth factor (VEGF), epithelial–mesenchymal transition (EMT) by E‐cadherin, metastasis by Igfbp‐4 and Tinagl1 enzyme‐linked immunosorbent assays, invasion by an invasion chamber, and apoptosis by Annexin V. Results The miR‐141 expression levels of MDA‐MB‐231 and MDA‐MB‐435 cells by administration of chitosan/mimic miR‐141 nanoplexes reached endogenous miR‐141 levels of a non‐tumorigenic epithelial breast cell line, MCF‐10A. According to our results, metastasis, VEGF, EMT and invasion in breast cancer cells were diminished, whereas apoptosis increased by 1.5‐ and 2.4‐fold in breast cancer cell lines as a result of the miR‐141 mimics. Conclusions In conclusion, we have demonstrated that administration of miR‐141 mimics at the determined doses to breast cancer cells revealed a tumor suppressor effect, and not the oncogenic face. The delivery of miR‐141 by chitosan nanoplexes presents a promising approach for the suppression of breast cancer.

Angioregulatory microRNAs in breast cancer: Molecular mechanistic basis and implications for therapeutic strategies

“…They also found that treatment with chitosan/miR‐141 nanoplexes significantly reduced the production of VEGF in these cells. However, chitosan/miR‐141 nanoplexes increased the expression levels of two metastatic factors, Tinagl1 and Igfbp‐4, in the BC cells and thus the role of miR-141 in the angiogenesis needs further investigation [84] . MiR-141 suppressed IL-8 and CXCL1 in basal-like BC which led to reduction in tumor growth and MVD [85] .…”

Therapeutic Silencing of BCL-2 Using NK Cell-Derived Exosomes as a Novel Therapeutic Approach in Breast Cancer

“…To overcome these issues, approaches like introduction of chemical modifications or loading siRNA into delivery vectors have been developed [ 19 , 59 ]. Previously, we used chitosan as a delivery vector to repress posttranscriptional vascular endothelial growth factor (VEGF) and zinc finger E-box binding homeobox (ZEB) expression, which resulted in inhibition of tumor angiogenesis and epithelial-mesenchymal transition (EMT) of breast cancer cells [ 60 , 61 , 62 ]. Even though chitosan has low cytotoxic, low bio-persistence, and mucoadhesive properties, weakness in intracellular dissociation and tumor cell specific targeting are still challenging problems, which reflects the necessity for improved delivery systems [ 63 ].…”

Chitosan Based MicroRNA Nanocarriers

“…Following the same trend, all studies were conducted on molar masses of CS ranging from 20-200 kDa to form intact biologically active nanoplexes [24,25,[36][37][38][39][40][41][42][43]. Exceptionally, few teams compared different molar masses in the same study, which gives more standardized results.…”

“…As demonstrated in Table 3 and Figure 10, CS miRNA NPs have been investigated mainly for cancer therapy [24,26,27,[33][34][35]37,41,42,53,56,[63][64][65][66][67][68]. Not only can that be attributed to the great characteristics of CS as a natural biocompatible biodegradable modifiable drug delivery system, but CS also has its own biological activities per se [4,92].…”