CHRNA7 and esophageal squamous cell carcinoma: Since it has been reported that metformin is capable of increasing DNA hypermethylation [25–27] and we have previously demonstrated that metformin possesses antineoplastic property toward ESCC [21, 28, 29], we decided to explore (1) if metformin can inhibit nicotine-induced CIC traits, (2) whether nicotine upregulates CHRNA7 in ESCC cells by altering promoter DNA methylation of CHRNA7 gene, and if so, (3) whether metformin can downregulate CHRNA7 by counteracting nicotine-mediated hypomethylation.