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miR-397a has been known to play a key role in plant development and in stress response by regulating mRNAs that code for the LAC2 in Arabidopsis.In this study, we had verified that miR-397a was highly expressed in leaf of safflower by small RNA sequencing technology.LAC2 targeted by miR-397a was down-regulated when miR-397a plasmid was transferred and over-expressed in the protoplast of safflower by qRT-PCR.These phenotypes illustrated LAC2 was negative regulated by miR-397a in safflower.