The study investigates the role of microRNA-101 (miR-101) in regulating the expression and function of Enhancer of Zeste Homolog 2 (EZH2), a histone methyltransferase involved in epigenetic silencing and cancer progression. MiR-101 is found to inhibit EZH2 expression and function in cancer cell lines. Analysis of human prostate tumors reveals that miR-101 expression decreases during cancer progression, while EZH2 expression increases. Somatic loss of one or both genomic loci encoding miR-101 is observed in a significant proportion of clinically localized and metastatic prostate cancers. The loss of miR-101 leads to overexpression of EZH2, resulting in dysregulation of epigenetic pathways and cancer progression. The study also demonstrates that miR-101 can reduce cell proliferation, invasion, and tumor growth in vitro and in vivo, and that it affects the epigenetic landscape by altering H3K27 tri-methylation and gene expression. The genomic loss of miR-101 may represent a progressive molecular lesion in the development of more aggressive cancer.The study investigates the role of microRNA-101 (miR-101) in regulating the expression and function of Enhancer of Zeste Homolog 2 (EZH2), a histone methyltransferase involved in epigenetic silencing and cancer progression. MiR-101 is found to inhibit EZH2 expression and function in cancer cell lines. Analysis of human prostate tumors reveals that miR-101 expression decreases during cancer progression, while EZH2 expression increases. Somatic loss of one or both genomic loci encoding miR-101 is observed in a significant proportion of clinically localized and metastatic prostate cancers. The loss of miR-101 leads to overexpression of EZH2, resulting in dysregulation of epigenetic pathways and cancer progression. The study also demonstrates that miR-101 can reduce cell proliferation, invasion, and tumor growth in vitro and in vivo, and that it affects the epigenetic landscape by altering H3K27 tri-methylation and gene expression. The genomic loss of miR-101 may represent a progressive molecular lesion in the development of more aggressive cancer.