Regulatory Roles of Noncoding RNAs in the Progression of Gastrointestinal Cancers and Health Disparities

Abstract

Annually, more than a million individuals are diagnosed with gastrointestinal (GI) cancers worldwide. With the advancements in radio- and chemotherapy and surgery, the survival rates for GI cancer patients have improved in recent years. However, the prognosis for advanced-stage GI cancers remains poor. Site-specific GI cancers share a few common risk factors; however, they are largely distinct in their etiologies and descriptive epidemiologic profiles. A large number of mutations or copy number changes associated with carcinogenesis are commonly found in noncoding DNA regions, which transcribe several noncoding RNAs (ncRNAs) that are implicated to regulate cancer initiation, metastasis, and drug resistance. In this review, we summarize the regulatory functions of ncRNAs in GI cancer development, progression, chemoresistance, and health disparities. We also highlight the potential roles of ncRNAs as therapeutic targets and biomarkers, mainly focusing on their ethnicity-/race-specific prognostic value, and discuss the prospects of genome-wide association studies (GWAS) to investigate the contribution of ncRNAs in GI tumorigenesis.

Keywords: biomarkers; chemoresistance; disparities; gastrointestinal cancers; noncoding RNAs; therapeutic targets.

Figure 1

NcRNA-mediated regulation of signal transduction pathways in GI cancer progression. Representative illustration of different ncRNA-mediated dysregulation of A. PI3K/AKT, B. Wnt/β-catenin, and C. TGF-β pathways. It should be noted that the ncRNA-mediated dysregulation of signal transduction pathways is not limited to the above pathways or ncRNAs; the red dotted line represents inhibition, and the red continuous frontal line represents activation by the respective ncRNA(s).