Regulation of Hippo, TGFβ/SMAD, Wnt/β-Catenin, JAK/STAT, and NOTCH by Long Non-Coding RNAs in Pancreatic Cancer

Abstract

Rapidly evolving and ever-increasing knowledge of the molecular pathophysiology of pancreatic cancer has leveraged our understanding altogether to a next level. Compared to the exciting ground-breaking discoveries related to underlying mechanisms of pancreatic cancer onset and progression, however, there had been relatively few advances in the therapeutic options available for the treatment. Since the discovery of the DNA structure as a helix which replicates semi-conservatively to pass the genetic material to the progeny, there has been conceptual refinement and continuous addition of missing pieces to complete the landscape of central dogma. Starting from transcription to translation, modern era has witnessed non-coding RNA discovery and central role of these versatile regulators in onset and progression of pancreatic cancer. Long non-coding RNAs (lncRNAs) have been shown to act as competitive endogenous RNAs through sequestration and competitive binding to myriad of microRNAs in different cancers. In this article, we set spotlight on emerging evidence of regulation of different signaling pathways (Hippo, TGFβ/SMAD, Wnt/β-Catenin, JAK/STAT and NOTCH) by lncRNAs. Conceptual refinements have enabled us to understand how lncRNAs play central role in post-translational modifications of various proteins and how lncRNAs work with epigenetic-associated machinery to transcriptionally regulate gene network in pancreatic cancer.

The interaction of canonical Wnt/β-catenin signaling with protein lysine acetylation

“…Particularly, WIF-1 and SFRPs directly interact with Wnts, and DKK blocks the FZD-LRP5/6 receptor complex to inhibit Wnt/β-catenin signaling [ 3 , 4 ]. Furthermore, numerous cellular factors, including protein kinases [ 5 ], non-coding RNA [ 6 ], and different posttranslational modifications (PTM) [ 7 ], including phosphorylation, sumoylation, and ubiquitination, are identified to play a vital role in modulating this signaling.…”

An Overview of Epigenetic Methylation in Pancreatic Cancer Progression

“…Functional experiments show that PRMT1 promotes PC cell proliferation in vitro and in vivo , and induces the upregulation of the β-catenin ( 68 ). The Wnt-β-catenin signaling pathway has already been highly implicated in pancreatic carcinogenesis and progression ( 69 ).…”

Crosstalk among long non-coding RNA, tumor-associated macrophages and small extracellular vesicles in tumorigenesis and dissemination

“…In addition to the ceRNA network, lncRNAs also directly regulate signaling molecules associated with the classical pathways of M2 polarization, such as the JAK/STAT signaling pathway. This pathway has been widely studied in many cancers including BC ( 70 ), cervical cancer ( 71 ), oral and gastric cancer ( 72 ), HCC ( 73 ), pancreatic cancer ( 74 ), lung cancer ( 75 ), glioblastoma ( 76 ), melanoma ( 77 ), leukemia ( 78 ), lymphoma ( 79 ), and myeloproliferative neoplasms ( 80 ).…”