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WRKY transcription factors, transcriptional regulators unique to plants, play an important role in defense response to pathogen infection. However, the resistance mechanisms of WRKY genes in sugarcane remain unclear. In the present study, gene ontology (GO) enrichment analysis revealed that WRKY gene family in sugarcane was extensively involved in the response to biotic stress and in defense response. We identified gene ScWRKY4, a class IIc member of the WRKY gene family, in sugarcane cultivar ROC22. This gene was induced by salicylic acid (SA) and methyl jasmonate (MeJA) stress. Interestingly, expression of ScWRKY4 was down-regulated in smut-resistant sugarcane cultivars but up-regulated in smutsusceptible sugarcane cultivars infected with Sporisorium scitamineum. Moreover, stable overexpression of the ScWRKY4 gene in Nicotiana benthamiana enhanced susceptibility to Fusarium solani var. coeruleum and caused down-regulated expression of immune marker-related genes. Transcriptome analysis indicated suppressed expression of most JAZ genes in the signal transduction pathway. ScWRKY4 interacted with ScJAZ13 to repress its expression. We thus hypothesized that the ScWRKY4 gene was involved in the regulatory network of plant disease resistance, most likely through the JA signaling pathway. The present study depicting the molecular involvement of ScWRKY4 in sugarcane disease resistance lays a foundation for future investigation. [ABSTRACT FROM AUTHOR]