The level of complexity within the network of interactions and correlative regulation of microRNAs (miRNA) and RNA-binding proteins (RBP) and their role in cancer has sparked new-found interest within the scientific community to study and target this process in modern cancer therapies. The post-transcriptional mechanisms mediated by RBPs and miRNAs and their role as key regulators in cancer make these types of proteins and molecules interesting targets for gene expression regulation and cancer therapy. Synthetic PNA-peptide hybrid molecules are novel hybrid molecules that have the potential to behave as synthetic miRNA mimics imitating the regulatory processes their natural counterparts take part in. From a chemical perspective and structurally speaking, PNA (peptide nucleic acid)-peptide hybrid molecules differ only slightly from natural miRNAs. Various synthetic approaches have been applied in the synthesis of PNA-peptide hybrids to imitate the natural miRNA structure such as the addition of charge on the back bone of the PNA component through use of γ-substituted PNA monomers. Cyclization of these types of molecules is also possible through our synthetic methods giving rise to various secondary structures. Binding assay experiments and preliminary data have demonstrated high binding affinity of these hybrids molecules to RBPs. Functional interactions between various known miRNAs and RBPs can thus be manipulated through the implementation and design of sequence specific PNA-peptide hybrid molecules. Sequencing technology and previous research efforts have contributed to extensive databases of the nucleotide sequences and structures of thousands of miRNAs and RBPs. This information provides the accessibility and possibility of designing and synthesizing PNA-peptide hybrid molecules to mimic or interact with a specific miRNA or RBP of interest.