Overexpression of KRAS enhanced the stemness of esophageal cancer cells inhibited by overexpression of circ0043898.

BACKGROUND: Our previous study revealed that circ0043898 is downregulated in esophageal cancer (EC), and its overexpression attenuates the progression of EC. The objective of this article is to explore whether circ0043898 inhibits tumor progression by inhibiting cancer stem cells (CSCs) in EC. METHODS: PCDH-circ0043898 plasmid was transfected into EC cells, and the effect of overexpression was verified by qRT-PCR. Immunofluorescence, flow cytometry, and stem cell spheroidization were used to detect CSCs phenotype changes. RNA sequencing was adopted to identify downstream regulatory genes and p-PI3K, PI3K, and KRAS expressions were validated by western blot. To investigate whether KRAS functions downstream of circ0043898 in regulating cancer stemness, we co-transfected EC cells with both KRAS and circ0043898 plasmids and examined CSCs phenotypes. RESULTS: circ0043898 was overexpressed in the EC cells, and reduced stem cell markers (CD44 and CD133) and the number of stem cell spheroidization. In addition, overexpression of circ0043898 changed many genes expression, including reduced p-PI3K, PI3K, and KRAS expressions. Moreover, overexpression of KRAS attenuated the effect of overexpressed circ0043898 on CSCs phenotype. CONCLUSIONS: Overexpression of circ0043898 reduced CSCs markers and the number of stem cell spheroidization. However, the overexpression of KRAS attenuated the inhibition effect of overexpressed circ0043898 on CSCs marker and the number of stem cell spheroidization. These findings identify a potential therapeutic target for the EC.