| خلاصه مقاله | Introduction
Hepatocellular carcinoma (HCC), a deadly form of liver cancer, is influenced by miRNAs and
imbalances in redox homeostasis. Cancer cells adapt themselves to high oxidative stress by
increasing self-antioxidant levels through the Nrf2/Keap1 pathway, but this can promote tumor
growth and drug resistance[1]. Human embryonic kidney cells (HEK-293) are considered a
suitable source of exosomes due to their transfection ease and lack of cancer-related
antigens[2, 3]. This study aims to investigate whether delivering miR-365a-3p through exosomes
can deactivate the antioxidant mechanism in HCC cells, potentially by increasing ROS levels[4].
Material and methods
After isolation of exosomes from HEK-293, they were loaded with miR-365a-3p mimic via
modified calcium chloride method. In order to evaluate the efficiency of the miR-365a-3p
encapsulation, quantitative real-time PCR was used. Next, the effect of the miR-365a-3p loaded
HEK-293 Exosomes on intracellular ROS, Nrf2, HO-1, and SOD1 protein, and Bcl2 mRNA levels
was investigated.
Results & Discussion
In vitro findings demonstrated that, ExomiR-365a-3p efficiently transfected in to cytoplasm of
HepG2 cells and significantly reduced the Nrf2, HO-1, and SOD1 protein level with inverse
augmentation of ROS levels. A significant population of exomiR-365a-3p treated cells showed
the intense decrease of Bcl2 as antiapoptotic factor. Taken together, Exosome-mediated delivery
of miR-365a-3p might induce apoptosis through decreasing Nrf2 pathway proteins level and
following increased oxidative stress in HepG2 cells. |