Mechanistic insights on the role of competing endogenous RNA regulatory networks (ceRNETs) in small cell lung cancer

Abstract

Small cell lung cancer (SCLC) is characterized by early metastatic dissemination and rapid emergence of chemoresistance resulting in a very dismal prognosis. SCLC tumors are characterized by nearly universal biallelic inactivation of TP53 and RB1 genes and are classified into four molecular subtypes based on the expression of lineage-specific transcription factors. The integration of information encoded by the coding and non-coding genome has significantly improved our understanding of the contribution of various non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), in the pathogenesis of SCLC. This has led to the concept of competing endogenous RNAs (ceRNAs) where the presence of the same miRNA response elements in one or more coding and ncRNAs may result in them competing for the same miRNA. Several studies have looked at the role of lncRNAs and circRNAs as ceRNAs by constructing ceRNA regulatory networks (ceRNETs). In this review, we discuss the role of ceRNETs in regulating various cancer hallmarks, including cell proliferation, invasion, migration, EMT, apoptosis, and chemoresistance of SCLC cells. We also discuss the potential of lncRNAs and circRNAs as biomarkers for diagnosis, prognosis, and predicting chemoresistance of SCLC.