Regulation of TGFβ/SMAD signaling by long non-coding RNAs in different cancers: Dark Knight in the Castle of molecular oncology

Abstract

One of the complex themes in recent years has been the multi-layered regulation of TGF beta signaling in cancer cells. TGF beta/SMAD signaling pathway is a highly complicated web of proteins which work spatio-temporally to regulate multiple steps of carcinogenesis. TGF beta/SMAD has been shown to dualistically regulate cancer progression. Therefore, TGF beta/SMAD signaling behaves as a "double-edged sword" in molecular oncology. Accordingly, regulation of TGF beta/SMAD is multi-layered because of oncogenic and tumor suppressor long non-coding RNAs (LncRNAs). In this review, we have summarized most recent breakthroughs in our understanding related to regulation of TGF beta/SMAD signaling by lncRNAs. We have comprehensively analyzed how different lncRNAs positively and negatively regulate TGF beta/SMAD signaling in different cancers. We have gathered missing pieces of an incomplete jig-saw puzzle of lncRNA-interactome ranging from "sponge effects" of lncRNAs to mechanistic modulation of TGF beta/SMAD signaling by lncRNAs.