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 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.

Automated summary

The multi-layered regulation of TGF beta/SMAD signaling in cancer cells involves complex interactions with oncogenic and tumor suppressor long non-coding RNAs (LncRNAs). These LncRNAs can either positively or negatively modulate the TGF beta/SMAD pathway in different types of cancer, making it a double-edged sword in molecular oncology. This review summarizes recent breakthroughs in understanding how LncRNAs regulate TGF beta/SMAD signaling, filling in missing pieces of the puzzle in the LncRNA-interactome.