Interaction between miRNAs and signaling cascades of Wnt pathway in chronic lymphocytic leukemia

Abstract

Chronic lymphocytic leukemia (CLL), a severe problem all over the world and represents around 25% of all total leukemia cases, is generating the need for novel targets against CLL. Wnt signaling cascade regulates cell proliferation, differentiation, and cell death processes. Thus, any alteration of the Wnt signaling pathway protein cascade might develop into various types of cancers, either by upregulation or downregulation of the Wnt signaling pathway protein components. In addition, it is reported that activation of the Wnt signaling pathway is associated with the transcriptional activation of microRNAs (miRNAs) by binding to its promoter region, suggesting feedback regulation. Considering the protein regulatory functions of various miRNAs, they can be approached therapeutically as modulatory targets for protein components of the Wnt signaling pathway. In this article, we have discussed the potential role of miRNAs in the regulation of Wnt signaling pathway proteins related to the pathogenesis of CLL via crosstalk between miRNAs and Wnt signaling pathway proteins. This might provide a clear insight into the Wnt protein regulatory function of various miRNAs and provide a better understanding of developing advanced and promising therapeutic approaches against CLL.

Molecular interactions of miR-338 during tumor progression and metastasis

“…WNT signaling is a pivotal pathway that regulates various cellular processes during embryogenesis and tumorigenesis. Regarding the post-transcriptional regulatory roles of miRNAs, they can be suggested as modulators of protein components in the WNT pathway [101][102][103]. Gastric cancer (GC) is the most frequent gastrointestinal malignancy and the leading cause of cancer-related mortality in developing countries [104].…”

The role of miRNAs as a big master regulator of signaling pathways involved in lymphoblastic leukemia

“…On the other hand, several findings have noted that some miRNAs are involved in the CLL and ALL pathogenesis intervening the WNT/βcatenin canonical signaling pathway (Bhattacharya et al, 2020;Weerkamp et al, 2006). Recently, it has been confirmed that miR-126 targets the GSK-3β gene and reduces its phosphorylation activity Abbreviations: ALL, acute lymphocytic leukemia; CLL, chronic lymphocytic leukemia; MADD, MAP-kinase activating death domain; mRNA, messenger RNA; miRNA, microRNA; NF-κB, nuclear factor kappa B; NRARP, NOTCH-regulated ankyrin repeat protein; PIK3R2, phosphoinositide-3-kinase, regulatory subunit 2; TGFB, transforming growth factor beta.…”

“…On the other hand, several findings have noted that some miRNAs are involved in the CLL and ALL pathogenesis intervening the WNT/β‐catenin canonical signaling pathway (Bhattacharya et al, 2020; Weerkamp et al, 2006). Recently, it has been confirmed that miR‐126 targets the GSK‐3β gene and reduces its phosphorylation activity in the CLL cells (Bhattacharya et al, 2020). The miR‐26a is another miRNA directly targeting the GSK‐3β gene.…”

“…The miR‐26a is another miRNA directly targeting the GSK‐3β gene. Moreover, this miRNA affects the β‐catenin expression level and its entry into the nucleus (Bhattacharya et al, 2020). Furthermore, miR‐34a plays a decisive role in WNT/β‐catenin canonical signaling pathway in CLL cells.…”

Proteomics and Drug Repurposing in CLL towards Precision Medicine

“…The therapy using CAR-T cells represents a recent therapeutic option for some CLL patients [ 40 , 41 ]. Finally, among the promising CLL therapies under investigation targeting several deregulated pathways are the cross-talk between CLL cells, the tumor microenvironment [ 42 , 43 ], the Wnt signaling pathway [ 44 ], various miRNAs [ 45 ], the Notch2 signaling pathway [ 46 ], the mitochondrial metabolism [ 16 ] and the epigenetic modifications [ 47 ].…”