Abstract: Provided herein are methods and compositions for the regulation of microRNA processing. The invention presents methods for inhibiting the activity of a Lin-28-like polypeptide and methods for treating a subject with cancer comprising administering to a subject with cancer a compound that inhibits the activity of a Lin-28-like polypeptide. Compositions comprise isolated polynucleotides and expression cassettes comprising the same that promote the processing of at least one of a regulated primary microRNA transcript by Drosha and a regulated precursor microRNA by Dicer when introduced into or expressed in a cell. Compositions and methods are also provided for the selective suppression of target polynucleotides by a microRNA based on the level of expression of a Lin-28-like polypeptide within a cell.