Exosome-mediated delivery of SCD-1 siRNA promoted the death of anaplastic thyroid carcinoma cells via regulating ROS level.
Anaplastic thyroid carcinoma (ATC)
Exosome
Reactive-oxygen species (ROS)
Stearoyl-CoA desaturase-1 (SCD-1)
Journal
Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico
ISSN: 1699-3055
Titre abrégé: Clin Transl Oncol
Pays: Italy
ID NLM: 101247119
Informations de publication
Date de publication:
Feb 2022
Feb 2022
Historique:
received:
21
05
2021
accepted:
08
07
2021
pubmed:
22
7
2021
medline:
11
3
2022
entrez:
21
7
2021
Statut:
ppublish
Résumé
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. 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. 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). 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.
Identifiants
pubmed: 34287816
doi: 10.1007/s12094-021-02682-x
pii: 10.1007/s12094-021-02682-x
doi:
Substances chimiques
RNA, Small Interfering
0
SCD1 protein, human
EC 1.14.19.1
Stearoyl-CoA Desaturase
EC 1.14.19.1
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
288-296Subventions
Organisme : National Natural Science Foundation of China
ID : No. 81873178
Organisme : Key disciplines Construction Project of Pudong Health Burea of Shanghai
ID : PWZxk2017-06
Organisme : Natural Science Foundation of Shanghai Science and Technology Commission
ID : No. 17ZR1421600
Organisme : Science and Technology Development Fund of Shanghai Pudong New Area
ID : No. PKJ2017-Y14
Organisme : Talents Training Program of Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine
ID : No. XX2017-06 and No. XX2017-04
Informations de copyright
© 2021. Federación de Sociedades Españolas de Oncología (FESEO).
Références
Schürch CM, Roelli MA, Forster S, Wasmer MH, Brühl F, Maire RS, Di Pancrazio S, Ruepp MD, Giger R, Perren A, et al. Targeting CD47 in anaplastic thyroid carcinoma enhances tumor phagocytosis by macrophages and is a promising therapeutic strategy. Thyroid. 2019;29:979–92.
doi: 10.1089/thy.2018.0555
Cao X, Dang L, Zheng X, Lu Y, Lu Y, Ji R, Zhang T, Ruan X, Zhi J, Hou X, et al. Targeting super-enhancer-driven oncogenic transcription by CDK7 inhibition in anaplastic thyroid carcinoma. Thyroid. 2019;29:809–23.
doi: 10.1089/thy.2018.0550
Molinaro E, Romei C, Biagini A, Sabini E, Agate L, Mazzeo S, Materazzi G, Sellari-Franceschini S, Ribechini A, Torregrossa L, et al. Anaplastic thyroid carcinoma: from clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol. 2017;13:644–60.
doi: 10.1038/nrendo.2017.76
Cabanillas ME, Zafereo M, Gunn GB, Ferrarotto R. Anaplastic thyroid carcinoma: treatment in the age of molecular targeted therapy. J Oncol Pract. 2016;12:511–8.
doi: 10.1200/JOP.2016.012013
Li Z, Zhang H. Reprogramming of glucose, fatty acid and amino acid metabolism for cancer progression. Cell Mol Life Sci. 2016;73:377–92.
doi: 10.1007/s00018-015-2070-4
Boroughs LK, DeBerardinis RJ. Metabolic pathways promoting cancer cell survival and growth. Nat Cell Biol. 2015;17:351–9.
doi: 10.1038/ncb3124
Beloribi-Djefaflia S, Vasseur S, Guillaumond F. Lipid metabolic reprogramming in cancer cells. Oncogenesis. 2016;5:e189.
doi: 10.1038/oncsis.2015.49
Ran H, Zhu Y, Deng R, Zhang Q, Liu X, Feng M, Zhong J, Lin S, Tong X, Su Q. Stearoyl-CoA desaturase-1 promotes colorectal cancer metastasis in response to glucose by suppressing PTEN. J Exp Clin Cancer Res. 2018;37:54.
doi: 10.1186/s13046-018-0711-9
Ducheix S, Peres C, Härdfeldt J, Frau C, Mocciaro G, Piccinin E, Lobaccaro JM, De Santis S, Chieppa M, Bertrand-Michel J, et al. Deletion of stearoyl-CoA desaturase-1 from the intestinal epithelium promotes inflammation and tumorigenesis reversed by dietary Oleate. Gastroenterology. 2018;155:1524–38.
doi: 10.1053/j.gastro.2018.07.032
Tracz-Gaszewska Z, Dobrzyn P. Stearoyl-CoA desaturase 1 as a therapeutic target for the treatment of cancer. Cancers. 2019;11:948.
doi: 10.3390/cancers11070948
Piao C, Cui X, Zhan B, Li J, Li Z, Li Z, Liu X, Bi J, Zhang Z, Kong C. Inhibition of stearoyl CoA desaturase-1 activity suppresses tumour progression and improves prognosis in human bladder cancer. J Cell Mol Med. 2019;23:2064–76.
doi: 10.1111/jcmm.14114
Liu G, Feng S, Jia L, Wang C, Fu Y, Luo Y. Lung fibroblasts promote metastatic colonization through upregulation of stearoyl-CoA desaturase 1 in tumor cells. Oncogene. 2018;37:1519–33.
doi: 10.1038/s41388-017-0062-6
von Roemeling CA, Marlow LA, Pinkerton AB, Crist A, Miller J, Tun HW, Smallridge RC, Copland JA. Aberrant lipid metabolism in anaplastic thyroid carcinoma reveals stearoyl CoA desaturase 1 as a novel therapeutic target. J Clin Endocrinol Metab. 2015;100:E697-709.
doi: 10.1210/jc.2014-2764
Srivastava A, Babu A, Filant J, Moxley KM, Ruskin R, Dhanasekaran D, Sood AK, McMeekin S, Ramesh R. Exploitation of exosomes as nanocarriers for gene-, chemo-, and immune-therapy of cancer. J Biomed Nanotechnol. 2016;12:1159–73.
doi: 10.1166/jbn.2016.2205
Das CK, Jena BC, Banerjee I, Das S, Parekh A, Bhutia SK, Mandal M. Exosome as a novel shuttle for delivery of therapeutics across biological barriers. Mol Pharm. 2019;16:24–40.
doi: 10.1021/acs.molpharmaceut.8b00901
Yoon YJ, Kim OY, Gho YS. Extracellular vesicles as emerging intercellular communicasomes. BMB Rep. 2014;47:531–9.
doi: 10.5483/BMBRep.2014.47.10.164
Liu H, Shen M, Zhao D, Ru D, Duan Y, Ding C, Li H. The effect of triptolide-loaded Exosomes on the proliferation and apoptosis of human ovarian cancer SKOV3 Cells. Biomed Res Int. 2019;2019:2595801.
pubmed: 31240207
pmcid: 6556367
Tkach M, Thery C. Communication by extracellular vesicles: where we are and where we need to go. Cell. 2016;164:1226–32.
doi: 10.1016/j.cell.2016.01.043
Liang G, Kan S, Zhu Y, Feng S, Feng W, Gao S. Engineered exosome-mediated delivery of functionally active miR-26a and its enhanced suppression effect in HepG2 cells. Int J Nanomed. 2018;13:585–99.
doi: 10.2147/IJN.S154458
Malhotra H, Sheokand N, Kumar S, Chauhan AS, Kumar M, Jakhar P, Boradia VM, Raje CI, Raje M. Exosomes: tunable nano vehicles for macromolecular delivery of transferrin and lactoferrin to specific intracellular compartment. J Biomed Nanotechnol. 2016;12:1101–14.
doi: 10.1166/jbn.2016.2229
Choi JS, Yoon HI, Lee KS, Choi YC, Yang SH, Kim IS, Cho YW. Exosomes from differentiating human skeletal muscle cells trigger myogenesis of stem cells and provide biochemical cues for skeletal muscle regeneration. J Control Release. 2016;222:107–15.
doi: 10.1016/j.jconrel.2015.12.018
Powers S, Pollack RE. Inducing stable reversion to achieve cancer control. Nat Rev Cancer. 2016;16:266–70.
doi: 10.1038/nrc.2016.12
Christy RJ, Yang VW, Ntambi JM, Geiman DE, Landschulz WH, Friedman AD, et al. Differentiation-induced gene expression in 3T3-L1 preadipocytes: CCAAT/enhancer binding protein interacts with and activates the promoters of two adipocyte-specific genes. Genes Dev. 1989;3:1323–35.
doi: 10.1101/gad.3.9.1323
Brown JM, Rudel LL. Stearoyl-coenzyme A desaturase 1 inhibition and the metabolic syndrome: considerations for future drug discovery. Curr Opin Lipidol. 2010;21:192–7.
doi: 10.1097/MOL.0b013e32833854ac
Currie E, Schulze A, Zechner R, Walther TC, Farese RV Jr. Cellular fatty acid metabolism and cancer. Cell Metab. 2013;18:153–61.
doi: 10.1016/j.cmet.2013.05.017
Piccinin E, Cariello M, De Santis S, Ducheix S, Sabbà C, Ntambi JM, Moschetta A. Role of Oleic acid in the gut-liver axis: from diet to the regulation of its synthesis via stearoyl-CoA desaturase 1 (SCD1). Nutrients. 2019;11:2283.
doi: 10.3390/nu11102283
Idelchik M, Begley U, Begley TJ, Melendez JA. Mitochondrial ROS control of cancer. Semin Cancer Biol. 2017;47:57–66.
doi: 10.1016/j.semcancer.2017.04.005
Chio IIC, Tuveson DA. ROS in cancer: the burning question. Trends Mol Med. 2017;23:411–29.
doi: 10.1016/j.molmed.2017.03.004
Gong TT, Guo Q, Li X, Zhang TN, Liu FH, He XH, et al. Isothiocyanate Iberin inhibits cell proliferation and induces cell apoptosis in the progression of ovarian cancer by mediating ROS accumulation and GPX1 expression. Biomed Pharmacother. 2021;2021:111533.
doi: 10.1016/j.biopha.2021.111533
Wang S, Hu Y, Yan Y, Cheng Z, Liu T. Sotetsuflavone inhibits proliferation and induces apoptosis of A549 cells through ROS-mediated mitochondrial-dependent pathway. BMC Complement Altern Med. 2018;18:235
Glasauer A, Chandel NS. Targeting antioxidants for cancer therapy. Biochem Pharmacol. 2014;92:90–101.
doi: 10.1016/j.bcp.2014.07.017
Olsen RK, Cornelius N, Gregersen N. Genetic and cellular modifiers of oxidative stress: what can we learn from fatty acid oxidation defects? Mol Genet Metab. 2013;110(Suppl):S31-39.
doi: 10.1016/j.ymgme.2013.10.007
Igal RA. Stearoyl CoA desaturase-1: new insights into a central regulator of cancer metabolism. Biochim Biophys Acta. 2016;1861:1865–80.
doi: 10.1016/j.bbalip.2016.09.009