Exosomes derived from microRNA-129-5p-modified tumor cells selectively enhanced suppressive effect in malignant behaviors of homologous colon cancer cells

Abstract

Exosome-encapsulated microRNAs (miRNAs) are novel diagnostic and predictive markers in colon cancer. Hence, the study of serum exosomal miRNAs in patients with colon cancer may help its diagnosis and treatment. PKH26-labeled exosomal uptake analysis identified whether exosomes transfer miRNA-129-5p to target cells. Transmission electron microscopy and dynamic light scattering analysis were applied to determine exosome morphology and size distribution. The Cell Counting Kit-8, wound healing assay and Transwell assays were used to detect cell proliferation, migration, and invasion after treatment with engineered exosomes. Moreover, the Western blotting was used to quantify the expression of proteins involved in cell apoptosis. In our study, hepatocellular liver carcinoma, cervical cancer and colon cancer cells were selected as the target cells of miRNA-129-5p exosomes. Exosomes containing miRNA-129-5p were found to be significantly more easily absorbed by colon cancer cells, presenting a stronger inhibitory effect on colon cancer cell proliferation. MiRNA-129-5p exosomes induced apoptosis in colon cancer cells while inhibiting their proliferation, migration, and invasion. In conclusion, exosomes derived from miRNA-129-5p-modified tumor cells selectively inhibited colon cancer progression, shedding new insights to therapeutic efficacy of this cancer.

Exosomal microRNAs in regulation of tumor cells resistance to apoptosis

“…Specifically, exosomes derived from tumor cells transfected with stable miRNA-129-5p exhibited selective apoptosis induction by decreasing Bcl-2 expression and increasing Bax expression. Additionally, these exosomes mitigated malignant characteristics associated with colon cancer [ 93 ].…”

Ferroptosis-Regulated Natural Products and miRNAs and Their Potential Targeting to Ferroptosis and Exosome Biogenesis

“…Ferroptosis-inducing miRNAs miR-101-3p [27] Medulloblastoma [250] RAB27A miR-1231 [225] Pancreatic ca [251] miR-1287-5p [226] Inflammatory injury [252] RAB7A miR-129-5p [243] Colon ca [253] VPS4B, ATP9A, PDCD6IP miR-142-3p [224] Retinoblastoma [254] STAM, HGS miR-143-3p [212] Lung ca [255], pancreatic ca [256] RAB7A miR-144-3p [234] Endothelial cells [257] VPS4B, PDCD6IP, SMPD3 miR-15a-5p [227] Endometrial ca [258], lung ca [259] MYO5B, VPS4A miR-15a-3p [228] Wound repair [260] miR-19b-3p [242] Lung ca [261] SDC1, VPS4B, MYO5B miR-28-5p [235] Lung injury [262 Ferroptosis-inhibiting miRNAs miR-18a-5p [248] Osteoblast cells [268] miR-19a-3p [21] Ischemic myocardium [269] SDC1, VPS4B, MYO5B miR-23a-3p [244] Cholangiocarcinoma [270] miR-424-5p [245] Endothelial cells [271] VPS4A, MYO5B miR-4291 [246] ATP9A, SMPD3, TSG101, MYO5B miR-522-3p [249] PDCD6IP miR-670-3p [247] CD34, RAB27A…”

“…Exosomal miRNA-1231 derived from bone marrow mesenchymal stem cells inhibits the proliferation and migration of pancreatic cancer cells [ 251 ]. Exosomal miR-129-5p inhibits the proliferation and migration of colon cancer cells [ 253 ]. Monocyte-derived exosomal miR-142-3p induces the antiproliferation of retinoblastoma cells [ 254 ].…”

Progress of regulatory RNA in small extracellular vesicles in colorectal cancer

“…Numerous studies have demonstrated that sEV-RncRNAs are involved in the regulation of the CRC anti-apoptotic signaling pathway in the tumor microenvironment, thereby inhibiting the proliferation of CRC cells and hindering their development (Nabariya et al, 2020). Ji et al (2021) found that miRNA-129-5p could be delivered to target cells via sEVs to inhibit CRC tumor invasion and migration and promote CRC cell apoptosis. Han et al (2021) found that sEVs loaded with anti-miRNA-221 oligonucleotides were taken up by colon cancer cells through NRP-1 protein and downregulated caco2 and HCT116 in CRC cells, which could inhibit CRC cell proliferation.…”