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MicroRNAs, a class of small non-coding RNAs, are believed to regulate several biological pathways and processes and are implicated in several diseases. They mostly regulate the levels of their target genes at the post transcriptional stage by primarily binding to the 3′ UTR. Elevated hepatic levels of miR-107 are a consistent feature associated with several obese and diabetic models. Here, we show that miR-107 post-transcriptionally regulates fatty acid synthase (FASN) by binding to its 3′ UTR and reduces its protein levels and the 3′UTR luciferase reporter activity, which are blunted by the miR-107 inhibitor and mutation in the miR-107 binding site in the 3′ UTR. Knock-down of endogenous miR-107 levels increased FASN levels in a dose-dependent manner. Overexpression of miR-107 led to significant accumulation of malonyl CoA, accompanied by ER stress induction. All these events were prevented in …