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

One of the complex themes in recent years has been the multi-layered regulation of TGFβ signaling in cancer cells. TGFβ/SMAD signaling pathway is a highly complicated web of proteins which work spatio-temporally to regulate multiple steps of carcinogenesis. TGFβ/SMAD has been shown to dualistically regulate cancer progression. Therefore, TGFβ/SMAD signaling behaves as a “double-edged sword” in molecular oncology. Accordingly, regulation of TGFβ/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 TGFβ/SMAD signaling by lncRNAs. We have comprehensively analyzed how different lncRNAs positively and negatively regulate TGFβ/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 TGFβ/SMAD signaling by lncRNAs.