The Regulatory Role of Non-coding RNAs on Programmed Cell Death Four in Inflammation and Cancer

Programmed cell death 4 (PDCD4) is a tumor suppressor gene implicated in many cellular functions, including transcription, translation, apoptosis, and the modulation of different signal transduction pathways. The downstream mechanisms of PDCD4 have been well-discussed, but its upstream regulators have not been systematically summarized. Noncoding RNAs (ncRNAs) are gene transcripts with no protein-coding potential but play a pivotal role in the regulation of the pathogenesis of solid tumors, cardiac injury, and inflamed tissue. In recent studies, many ncRNAs, especially microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), were found to interact with PDCD4 to manipulate its expression through transcriptional regulation and function as oncogenes or tumor suppressors. For example, miR-21, as a classic oncogene, was identified as the key regulator of PDCD4 by targeting its 3'-untranslated region (UTR) to promote tumor proliferation, migration, and invasion in colon, breast, and bladder carcinoma. Therefore, we reviewed the recently emerging pleiotropic regulation of PDCD4 by ncRNAs in cancer and inflammatory disorders and aimed to shed light on the mechanisms of associated diseases, which could be conducive to the development of novel treatment strategies for PDCD4-induced diseases.