Role of Hedgehog and Hippo signaling pathways in cancer: A special focus on non-coding RNAs

Abstract

Despite advanced clinical and translational oncology research, mortality rates are still increasing worldwide. Recently, a class of non-coding RNAs (ncRNAs), such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been well investigated in regulating biological, molecular, and cellular signaling pathways. This review article provided the current research progress on how miRNAs, lncRNAs, and circRNAs regulate Hedgehog (Hh) and Hippo signaling pathways in various cancers. These ncRNAs target both pathways' key downstream molecules and may be used for targeted cancer treatment. Moreover, Hh and Hippo signaling pathways crosstalked with each other through Gli1 of Hh pathways and YAP1/TEAD molecules of Hippo pathways during cancer progression. Additionally, Hh and Hippo signaling pathways regulate resistance against the chemo, radio, and immune therapies for several types of cancer via inducing GLI and YAP/TAZ proteins level. Therefore, to improve the treatment regime, we presented the role of various prominent phytochemicals such as curcumin, resveratrol, genistein, quercetin, paclitaxel, and silibinin in regulating lncRNAs, miRNAs, circRNA through Hedgehog and Hippo signaling pathways' constituents in cancers. We believe that knowledge obtained from this review may help make new drugs for cancer treatment in the future.

Keywords: Cancer; Circular RNA; Drug; Hedgehog; Hippo; LncRNAs; MiRNAs; Non-coding RNA; Signaling pathways.