miRNAs and the Hippo pathway in cancer: Exploring the therapeutic potential (Review)

Abstract

Cancer is recognized as the leading cause of death worldwide. The hippo signaling pathway regulates organ size by balancing cell proliferation and cell death; hence dysregulation of the hippo pathway promotes cancer-like conditions. miRNAs are a type of non-coding RNA that have been shown to regulate gene expression. miRNA levels are altered in various classes of cancer. Researchers have also uncovered a crosslinking between miRNAs and the hippo pathway, which has been linked to cancer. The components of the hippo pathway regulate miRNA synthesis, and various miRNAs regulate the components of the hippo pathway both positively and negatively, which can lead to cancer-like conditions. In the present review article, the mechanism behind the hippo signaling pathway and miRNAs biogenesis and crosslinks between miRNAs and the hippo pathway, which result in cancer, shall be discussed. Furthermore, the article will cover miRNA-related therapeutics and provide an overview of the development of resistance to anticancer drugs. Understanding the underlying processes would improve the chances of developing effective cancer treatment therapies.

Malignant mesothelioma tumours: molecular pathogenesis, diagnosis, and therapies accompanying clinical studies

“…A lack of the Hippo pathway’s activation enables the YAP1/TAZ to get enter the nucleus and serve as the coactivators for the transcription of genes. The transcription factor YAP1/TAZ interacts with TEA domain transcription factors, SMADs, T-Box 5 (TBX5), Runt related transcription factor (RUNX), p73, early growth response-1 (EGR1) and the carboxyl-terminal fragment of Erb-B2 receptor tyrosine kinase 4 (ERBB4) transcription factors ( 45 ). Through its actions on cell junction-associated proteins which impart a chief role in the regulation of the Hippo signaling, Merlin stimulates the Hippo pathway and inhibits YAP1/TAZ as well ( 46 ).…”

The Hippo signalling pathway and its impact on eye diseases

“…8 Since YAP/TAZ lack DNA-binding sites, they exert their biological effects by forming complexes with various transcription factors, including TEA domain DNA-binding family members (TEAD1-4), SMADs and the Runt-related transcription factor (RUNX) family. 9,10 The expression of downstream target genes of the Hippo pathway, such as connective tissue growth factor (CTGF), 11 cysteine-rich angiogenic inducer 61 (CYR61), 11 ankyrin repeat domain 1 (ANKRD1), 12 and MYC proto-oncogene bHLH transcription factor (MYC), 13 regulates cell proliferation and survival. The Hippo signalling system has been demonstrated to be critical in embryonic development.…”

“…On the other hand, when the Hippo pathway is inactivated, dephosphorylated YAP/TAZ enters the nucleus where they interact with other transcription factors to regulate downstream gene transcription 8 . Since YAP/TAZ lack DNA‐binding sites, they exert their biological effects by forming complexes with various transcription factors, including TEA domain DNA‐binding family members (TEAD1‐4), SMADs and the Runt‐related transcription factor (RUNX) family 9,10 . The expression of downstream target genes of the Hippo pathway, such as connective tissue growth factor (CTGF), 11 cysteine‐rich angiogenic inducer 61 (CYR61), 11 ankyrin repeat domain 1 (ANKRD1), 12 and MYC proto‐oncogene bHLH transcription factor (MYC), 13 regulates cell proliferation and survival.…”

Editorial: MicroRNAs in endocrinology and cell signaling

“…For example, many miRNAs are known to target androgen, estrogen, and progestin receptors ( 16 ). Cellular signaling pathways, such as TGFβ/SMAD ( 17 , 18 ), MAPK ( 19 ), Wnt/β-catenin ( 20 ), PI3K/AKT ( 21 ) and others ( 22 , 23 ) are extensively modulated by miRNAs. On the other hand, many hormones and intracellular signaling pathways can also regulate miRNA levels.…”