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07-12-2022 | Pancreatic Cancer | Research Paper

Nanoparticles loaded with circ_0086375 for suppressing the tumorigenesis of pancreatic cancer by targeting the miR-646/SLC4A4 axis

Authors: Yunjian Wang, Min Zhang, Luyang Zhang, Minghe Zhou, Enze Wang

Published in: Clinical & Experimental Metastasis | Issue 1/2023

Abstract

Nanoparticles possess the ability to adsorb and load other compounds. This study aimed to synthesize a gene carrier with polyethyleneimine (PEI), hyaluronic acid (HA) and mesoporous silica nanoparticles (MSNs) for circ_0086375 delivery to investigate the role and mechanism of circ_0086375 in pancreatic cancer (PC) progression. The expression of genes and proteins was detected by quantitative real-time polymerase chain reaction and Western blot. In vitro experiments were performed by cell counting Kit-8 (CCK-8), 5-Ethynyl-2′-deoxyuridine (EdU) assay, flow cytometry, transwell assay, and wound healing assay, respectively. Dual-luciferase activity assay was used to investigate the target relationship between miR-646 and circ_0086375 or SLC4A4 (solute carrier family 4 member 4). Circ_0086375 loaded PEI/HA-based mesoporous silica nanoparticles (MSNs) were prepared, and in vivo assay was performed by using xenograft tumor model. Circ_0086375 expression was decreased in PC tissues and cells. Restoration of circ_0086375 suppressed PC cell proliferation, migration and invasion in vitro and in vivo. Mechanistically, circ_0086375 acted as a sponge for miR-646 to elevate SLC4A4 expression, which was confirmed to be a target of miR-646. The prepared circ_0086375/MSN/PEI/HA nanocomplexes showed excellent fluorescent properties and a higher cellular uptake of circ_0086375 in PC cells. Moreover, circ_0086375/MSN/PEI/HA showed relatively more anticancer effects in PC than that of circ_0086375 alone in vitro and in vivo. Delivery of circ_0086375 by nanoparticles suppresses the tumorigenicity of pancreatic cancer by miR-646/SLC4A4 axis, suggesting a new potential target for future pancreatic cancer treatment.

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Title: Nanoparticles loaded with circ_0086375 for suppressing the tumorigenesis of pancreatic cancer by targeting the miR-646/SLC4A4 axis
Authors: Yunjian Wang
Min Zhang
Luyang Zhang
Minghe Zhou
Enze Wang
Publication date: 07-12-2022
Publisher: Springer Netherlands
Keywords: Pancreatic Cancer
Pancreatic Cancer
Published in: Clinical & Experimental Metastasis / Issue 1/2023
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI: https://doi.org/10.1007/s10585-022-10197-0

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