One of the hallmarks of cancer is metastasis, a process that entails the spread of cancer cells to distant regions in the body, culminating in tumor formation in secondary organs. Importantly, the proinflammatory environment surrounding cancer cells further contributes to cancer cell transformation and extracellular matrix destruction. During metastasis, front-rear polarity and emergence of migratory and invasive features are manifestations of epithelial-mesenchymal transition (EMT). A variety of transcription factors (TFs) are implicated in the execution of EMT, the most prominent belonging to the Snail Family Transcriptional Repressor (SNAI) and Zinc Finger E-Box Binding Homeobox (ZEB) families of TFs. These TFs are regulated by interaction with specific microRNAs (miRNAs), as miR34 and miR200. Among the several secondary metabolites produced in plants, flavonoids constitute a major group of bioactive molecules, with several described effects including antioxidant, antiinflammatory, antidiabetic, antiobesogenic, and anticancer effects. This review scrutinizes the modulatory role of flavonoids on the activity of SNAI/ZEB TFs and on their regulatory miRNAs, miR-34, and miR-200. The modulatory role of flavonoids can attenuate mesenchymal features and stimulate epithelial features, thereby inhibiting and reversing EMT. Moreover, this modulation is concomitant with the attenuation of signaling pathways involved in diverse processes as cell proliferation, cell growth, cell cycle progression, apoptosis inhibition, morphogenesis, cell fate, cell migration, cell polarity, and wound healing. The antimetastatic potential of these versatile compounds is emerging and represents an opportunity for the synthesis of more specific and potent agents.

ZEB1 Antisense RNA 1 (ZEB1-AS1) is a type of RNA characterized as long non-coding RNA (lncRNA). This lncRNA has important regulatory roles on its related gene, Zinc Finger E-Box Binding Homeobox 1 (ZEB1). In addition, role of ZEB1-AS1 has been approved in diverse malignancies such as colorectal cancer, breast cancer, glioma, hepatocellular carcinoma and gastric cancer. ZEB1-AS1 serves as a sponge for a number of microRNAs, namely miR-577, miR-335-5p, miR-101, miR-505-3p, miR-455-3p, miR-205, miR-23a, miR-365a-3p, miR-302b, miR-299-3p, miR-133a-3p, miR-200a, miR-200c, miR-342-3p, miR-214, miR-149-3p and miR-1224-5p. In addition to malignant conditions, ZEB1-AS1 has functional role in non-malignant conditions like diabetic nephropathy, diabetic lung, arthrosclerosis, Chlamydia trachomatis infection, pulmonary fibrosis and ischemic stroke. This review outlines different molecular mechanisms of ZEB1-AS1 in a variety of disorders and highlights its importance in their pathogenesis.