Details

Autor(en) / Beteiligte

• Abdel-Latif, Mustafa
• Riad, Ahmed
• Soliman, Raghda A.
• Elkhouly, Aisha M.
• Nafae, Heba
• Gad, Mohamed Z.
• Motaal, Amira Abdel
• Youness, Rana A.

Titel

MALAT-1/p53/miR-155/miR-146a ceRNA circuit tuned by methoxylated quercitin glycoside alters immunogenic and oncogenic profiles of breast cancer

Ist Teil von

• Molecular and cellular biochemistry, 2022-04, Vol.477 (4), p.1281-1293

Ort / Verlag

New York: Springer US

Erscheinungsjahr

2022

Link zum Volltext

Quelle

SpringerLink

Beschreibungen/Notizen

• Triple-Negative Breast Cancer (TNBC) is one of the most aggressive and hot BC subtypes. Our research group has recently shed the light on the utility of natural compounds as effective immunotherapeutic agents. The aim of this study is to investigate the role of a methoxylated quercetin glycoside (MQG) isolated from Cleome droserifolia in harnessing TNBC progression and tuning the tumor microenvironment and natural killer cells cytotoxicity. Results showed that MQG showed the highest potency (IC 50  = 12 µM) in repressing cellular proliferation, colony-forming ability, migration, and invasion capacities. Mechanistically, MQG was found to modulate a circuit of competing endogenous RNAs where it was found to reduce the oncogenic MALAT-1 lncRNA and induce TP53 and its downstream miRNAs; miR-155 and miR-146a. Accordingly, this leads to alteration in several downstream signaling pathways such as nitric oxide synthesizing machinery, natural killer cells' cytotoxicity through inducing the expression of its activating ligands such as MICA/B, ULBP2, CD155, and ICAM-1 and trimming of the immune-suppressive cytokines such as TNF-α and IL-10. In conclusion, this study shows that MQG act as a compelling anti-cancer agent repressing TNBC hallmarks, activating immune cell recognition, and alleviating the immune-suppressive tumor microenvironment experienced by TNBC patients.