The Interplay between Noncoding RNAs and p21 Signaling in Gastrointestinal Cancer: From Tumorigenesis to Metastasis

Abstract

Non-coding RNAs (ncRNAs) are emerging as important regulators in various pathological conditions, including human cancers. NcRNAs exert potentially crucial effects on cell cycle progression, proliferation, and invasion in cancer cells by targeting various cell cycle-related proteins at transcriptional and post-transcriptional levels. As one of the key cell cycle regulatory proteins, p21 is involved in various processes, including the cellular response to DNA damage, cell growth, invasion, metastasis, apoptosis, and senescence. P21 has been shown to have either a tumor-suppressive or oncogenic effect depending on the cellular localization and posttranslational modifications. P21 exerts a significant regulatory effect on both G1/S and G2/M checkpoints by regulating the function of cyclin-dependent kinase enzymes (CDKs) or interacting with proliferating cell nuclear antigen (PCNA). P21 has an important effect on the cellular response to DNA damage by separating DNA replication enzymes from PCNA and inhibiting DNA synthesis resulting in G1 phase arrest. Furthermore, p21 has been shown to negatively regulate the G2/M checkpoint through the inactivation of cyclin-CDK complexes. In response to any cell damage caused by genotoxic agents, p21 exerts its regulatory effects by nuclear preservation of cyclin B1-CDK1 and preventing their activation. Notably, several ncRNAs, including lncRNAs and miRNAs, have been shown to be involved in tumor initiation and progression through the regulation of the p21 signaling axis. In this review, we discuss the miRNA/lncRNA-dependent mechanisms that regulate p21 and their effects on gastrointestinal tumorigenesis. A better understanding of the regulatory effects of ncRNAs on the p21 signaling may help to discover novel therapeutic targets in gastrointestinal cancer.

Evaluation of common protein biomarkers involved in the pathogenesis of respiratory diseases with proteomic methods: A systematic review

“…LXA4 has been shown to regulate pulmonary epithelial cells by regulating tight junctions and preventing inflammation. However, LXA4 reduces tissue factor (TF) expression by inhibiting the TNF‐α/PI3K/AKT pathway 170–174 . TF is the starting factor in the coagulation cascade, the word of which can cause thrombosis.…”

“…Studies have shown that TGF‐β causes inflammation and airway obstruction by activating actin in epithelial cells 177 . On the other hand, TGF‐β stimulates epithelial‐mesenchymal transition (EMT) to produce inflammatory mediators, including cytokines; they can affect pulmonary epithelial cells’ function 178–181 …”

“…However, LXA4 reduces tissue factor (TF) expression by inhibiting the TNF-α/PI3K/AKT pathway. [170][171][172][173][174] TF is the starting factor in the coagulation cascade, the word of which can cause thrombosis. Increased C3 expression in IPF leads to activation of the TGF-β/SMAD pathway, which ultimately causes lung fibrosis.…”

“…177 On the other hand, TGF-β stimulates epithelial-mesenchymal transition (EMT) to produce inflammatory mediators, including cytokines; they can affect pulmonary epithelial cells' function. [178][179][180][181] However, ApoA1 in IPF has been shown to prevent inflammation by inhibiting TGF-β expression. ApoA1 also inhibits inflammation and inflammatory cytokines production by inhibiting NF-κB.…”

Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy

“…Targeting these interactions may provide novel therapeutic opportunities for cancer treatment. The cancer cell-of-origin hypothesis has revolutionized our understanding of tumor initiation and progression [ 523 ]. By identifying the specific cells from which cancers originate, researchers have made significant strides in deciphering the underlying mechanisms of various malignancies.…”