This technology includes a method to identify potentially therapeutic microRNAs in cancer, particularly squamous cell carcinoma of the head and neck (HNSCC). This approach first utilizes a large and publicly available expression dataset, which is then validated by a smaller independent dataset to determine deregulated microRNAs expression. These results are then intersected with in vitro functional anti-proliferative screening data to select for microRNAs that play a functional tumor suppressive role and likely serve as therapeutic targets. Utilizing the recently published data from 279 tumor specimens, this analysis strategy identified 9 potentially therapeutic microRNAs, four of which were members of the miR-30-5p family. To further validate its role in tumor suppression, several classical oncogenes centering on Receptor tyrosine kinase (RTK) signaling as novel targets of miR-30 and display regulation both in vitro and in vivo were identified. Finally, its validity as a therapeutic target is supported by showing strong tumor growth delay for a synthetic miR-30a-5p mimic in a xenograft tumor model of HNSCC.