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Review
. 2023 Sep 27:14:1269233.
doi: 10.3389/fphar.2023.1269233. eCollection 2023.

Unlocking the role of non-coding RNAs in prostate cancer progression: exploring the interplay with the Wnt signaling pathway

Tong Bu  1 , Le Li  1 , Jiyu Tian  1
Affiliations
Review

Unlocking the role of non-coding RNAs in prostate cancer progression: exploring the interplay with the Wnt signaling pathway

Tong Bu et al. Front Pharmacol. .

Abstract

Prostate cancer (PCa) is one of the most common cancers in males, exhibiting a wide spectrum of clinical manifestations that pose challenges in its diagnosis and treatment. The Wnt signaling pathway, a conserved and complex pathway, is crucial for embryonic development, tissue homeostasis, and various physiological processes. Apart from the classical Wnt/β-catenin signaling pathway, there exist multiple non-classical Wnt signaling pathways, including the Wnt/PCP and Wnt/Ca2+ pathways. Non-coding RNAs (ncRNAs) are involved in the occurrence and development of PCa and the response to PCa treatment. ncRNAs are known to execute diverse regulatory roles in cellular processes, despite their inability to encode proteins. Among them, microRNAs, long non-coding RNAs, and circular RNAs play key roles in the regulation of the Wnt signaling pathway in PCa. Aberrant expression of these ncRNAs and dysregulation of the Wnt signaling pathway are one of the causes of cell proliferation, apoptosis, invasion, migration, and angiogenesis in PCa. Moreover, these ncRNAs affect the characteristics of PCa cells and hold promise as diagnostic and prognostic biomarkers. Herein, we summarize the role of ncRNAs in the regulation of the Wnt signaling pathway during the development of PCa. Additionally, we present an overview of the current progress in research on the correlation between these molecules and clinical features of the disease to provide novel insights and strategies for the treatment of PCa.

Keywords: Wnt signaling pathway; circRNA; lncRNA; miRNA; non-coding RNA; prostate cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The diverse types and molecular mechanisms of the Wnt signaling pathway. This diagram illustrates the classification and members of the Wnt signaling pathway. The Wnt signaling pathway can be categorized into three classes: (1) Wnt/β-catenin signal transduction, (2) Wnt/PCP signal transduction, (3) Wnt/Ca2+ signal transduction. In the Wnt/β-catenin pathway, Wnt ligands bind to Frizzled receptors and LRP co-receptors, leading to the activation of the disheveled protein and subsequent inactivation of Axin protein. This results in the accumulation of β-catenin in the cytoplasm, its translocation into the nucleus, and binding to TCF/LEF transcription factors, ultimately inducing downstream gene expression. Wnt/PCP signaling pathway involved in cell polarity, tissue morphogenesis, cell adhesion, and directional migration through JNK and Rho GTPase signaling pathways. The Wnt/Ca2+ signaling pathway modulates gene expression and cell behavior by regulating intracellular Ca2+ levels. Abbreviations: Wnt, Wingless-related integration site; LRP, Low-density lipoprotein receptor-related protein; GSK3β, Glycogen Synthase Kinase 3 beta; CKIα, Casein kinase I alpha; Axin, Axis inhibitor; APC, Adenomatous Polyposis Coli; TCF, T-cell factor; LEF, Lymphoid enhancer-binding factor; RAC1, Ras-related C3 botulinum toxin substrate 1; DAMM1, Disheveled-associated activator of morphogenesis 1; JNK, c-Jun N-terminal kinase; RhoA, Ras homolog family member A; c-JUN, Cellular Jun oncogene; ROCK2, Rho-associated coiled-coil kinase 2; AP-1, Activator protein 1; PIP2, Phosphatidylinositol 4,5-bisphosphate; IP3, Inositol trisphosphate; DAG, Diacylglycerol; CDC42, Cell division control protein 42 homolog; TAK1, Transforming growth factor-beta-activated kinase 1; CAMKII, Ca2+/calmodulim-dependent protein kinase II; NFAT, Nuclear factor of activated T-cells.
FIGURE 2
FIGURE 2
The involvement of ncRNAs in modulating the Wnt signaling pathway in prostate cancer. This diagram illustrates the involvement of ncRNAs in modulating the Wnt signaling pathway in PCa. Blue represents the role of suppressing the Wnt signaling pathway. Red represents roles that facilitate the Wnt signaling pathway.
FIGURE 3
FIGURE 3
Role of Wnt signaling pathway-related ncRNAs in the regulation of invasion and migration in prostate cancer. This diagram illustrates the role of Wnt signaling pathway-related ncRNAs in the regulation of invasion and migration in PCa. Blue represents the role of suppressing the Wnt signaling pathway. Red represents roles that facilitate the Wnt signaling pathway.
FIGURE 4
FIGURE 4
Role of Wnt signaling pathway-related ncRNAs in the regulation of EMT, apoptosis, stemness, and CRPC formation in prostate cancer. This diagram illustrates the role of Wnt signaling pathway-related ncRNAs in the regulation of EMT, apoptosis, stemness, and CRPC formation in PCa. Blue represents the role of suppressing the Wnt signaling pathway. Red represents roles that facilitate the Wnt signaling pathway.
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