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Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level.

AbstractPURPOSE:
Anaplastic thyroid carcinoma (ATC) is one of the most aggressive cancers in the world. Stearoyl-CoA desaturase-1 (SCD-1) is one of major enzymes in the de novo synthesis of fatty acids and is related to cancer aggressiveness and poor patient prognosis. The study aimed to construct exosomes loaded SCD-1 interference, investigate its effects and mechanisms on the cell proliferation and apoptosis of ATC cells.
METHODS:
The expressions of SCD-1 in normal thyroid cell line and ATC cell lines were determined by qRT-PCR and western blotting, respectively. Exosomes were prepared and purification then loaded with SCD-1 siRNA by electroporation and observed by transmission electron microscopy. Higher SCD-1 mRNA and protein levels were found in ATC cell lines compared than normal thyroid cell line (P < 0.05), and both Hth-7 and FRO cells could uptake PKH67-labeled exosomes. The effects of exosomes loaded SCD-1 siRNA on ATC cells were measured by CCK8 assay and apoptosis detection kit.
RESULTS:
When compared with control group, the cell viability significantly decreased in both two ATC cell lines taken up exosomes loaded SCD-1 siRNA (P < 0.001), and apoptotic and necrotic cells obviously increased (P < 0.05). In order to explore the mechanism of exosomes loaded SCD-1 on ATC, the ROS level was detected by fluorescence reagent. It was found that exosomes loaded SCD-1 siRNA significantly increased intracellular ROS level of ATC cells (P < 0.05).
CONCLUSIONS:
Exosomes loaded SCD-1 siRNA inhibited ATC cellular proliferation and promoted cellular apoptosis, and the mechanisms involved maybe the regulation of fatty acids metabolism and ROS level. Our study provides a promising therapeutic strategy for ATC.
AuthorsM H Wang, Y Ye, M Zhang, B R Zhou, J N Wang, Y N Song, W Xia
JournalClinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico (Clin Transl Oncol) Vol. 24 Issue 2 Pg. 288-296 (Feb 2022) ISSN: 1699-3055 [Electronic] Italy
PMID34287816 (Publication Type: Journal Article)
Copyright© 2021. Federación de Sociedades Españolas de Oncología (FESEO).
Chemical References
  • RNA, Small Interfering
  • SCD1 protein, human
  • Stearoyl-CoA Desaturase
Topics
  • Apoptosis
  • Cell Proliferation
  • Exosomes (physiology)
  • Humans
  • RNA, Small Interfering (physiology)
  • Stearoyl-CoA Desaturase (metabolism)
  • Thyroid Carcinoma, Anaplastic (pathology)
  • Thyroid Neoplasms (pathology)
  • Tumor Cells, Cultured

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