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Recent evidence also demonstrates the dual role of nicotine, which primarily promotes hepatocarcinogenesis through activation of multiple oncogenic signaling cascades, including 7-nicotinic acetylcholine receptor (7-nAChR)/JAK2/STAT3, CYP1A1/PI3K/Akt signaling mediated by NF-B and AP-1, SETDB1/CDK6-mediated STAT1 stabilization, GCF2-driven Wnt/-catenin/SOX2 signaling, and the 2-adrenergic receptor (2-AR)/PI3K/Akt pathway [35,36,37]