MicroRNA-373 induces gene expression by targeting complementary sequences in gene promoters. This study demonstrates that miRNA can not only repress gene expression but also induce it by binding to promoter regions. Using in silico analysis, the researchers identified a putative miR-373 target site in the E-cadherin promoter. Transfection of miR-373 and its precursor (pre-miR-373) into PC-3 cells significantly increased E-cadherin expression. Knockdown experiments confirmed that miR-373-induced E-cadherin expression required the miRNA maturation protein Dicer. Additionally, the cold-shock domain-containing protein C2 (CSDC2), which also contains a putative miR-373 target site in its promoter, was induced by miR-373 and pre-miR-373. RNA polymerase II enrichment was detected at both E-cadherin and CSDC2 promoters after miR-373 transfection, indicating that miR-373 enhances gene expression by promoting transcription. Sequence specificity was confirmed by showing that mutations to miR-373 reduced gene induction. Transfection of promoter-specific dsRNAs revealed that miR-373-induced expression of E-cadherin and CSDC2 required target sites in both promoters. These findings suggest that miRNAs can regulate gene expression by targeting promoter sequences, revealing a new mechanism of miRNA function. The study also highlights the differential activation of target genes in different cell lines, indicating that miRNA effects may depend on cellular context. Overall, the results demonstrate that miRNAs can induce gene expression by binding to promoter regions, expanding the known roles of miRNAs in gene regulation.MicroRNA-373 induces gene expression by targeting complementary sequences in gene promoters. This study demonstrates that miRNA can not only repress gene expression but also induce it by binding to promoter regions. Using in silico analysis, the researchers identified a putative miR-373 target site in the E-cadherin promoter. Transfection of miR-373 and its precursor (pre-miR-373) into PC-3 cells significantly increased E-cadherin expression. Knockdown experiments confirmed that miR-373-induced E-cadherin expression required the miRNA maturation protein Dicer. Additionally, the cold-shock domain-containing protein C2 (CSDC2), which also contains a putative miR-373 target site in its promoter, was induced by miR-373 and pre-miR-373. RNA polymerase II enrichment was detected at both E-cadherin and CSDC2 promoters after miR-373 transfection, indicating that miR-373 enhances gene expression by promoting transcription. Sequence specificity was confirmed by showing that mutations to miR-373 reduced gene induction. Transfection of promoter-specific dsRNAs revealed that miR-373-induced expression of E-cadherin and CSDC2 required target sites in both promoters. These findings suggest that miRNAs can regulate gene expression by targeting promoter sequences, revealing a new mechanism of miRNA function. The study also highlights the differential activation of target genes in different cell lines, indicating that miRNA effects may depend on cellular context. Overall, the results demonstrate that miRNAs can induce gene expression by binding to promoter regions, expanding the known roles of miRNAs in gene regulation.