MALAT-1/p53/miR-155/miR-146a ceRNA circuit tuned by Methoxylated Quercitin Glycoside Alters Immunogenic and Oncogenic Profiles of Breast cancer

Abstract Triple Negative Breast Cancer (TNBC) is one of the most aggressive and hot BC subtypes. Our research group has recently shed the light onto the utility of natural compounds as effective immunotherapeutic agents. The aim of this study is to investigate the role of a methoxylated quercitin 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 highest potency 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 induced TP53 and its downstream miRNAs; miR-155 and miR-146a. In turn, this lead to alteration in several downstream signaling pathways such as nitric oxide machinery, natural killer cells 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.