The role of miRNAin prostate cancer diagnosis, prognosisand treatment response: a narrative review

Vazquez-Urrutia, Jorge Raul; Torres-Bustamante, Maria Iyali; Cerda-Cruz, Cesar Rodrigo; Bravo-Cuéllar, Alejandro; Ortiz‐Lazareno, Pablo César

doi:10.2217/fon-2022-0891

Cited by 4 publications

(1 citation statement)

References 107 publications

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“…Many patients with PCa are diagnosed using prostate biopsy and pathological analyses 34 . Unfortunately, current screening methods for detecting early disease lack sufficient sensitivity and specificity, leading to unnecessary biopsies and overtreatment 35 . In particular, the use of PSA for population screening has been controversial since the protein was first purified 36 .…”

Section: Discussionmentioning

confidence: 99%

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis

Zhang,

Yu,

Bai

et al. 2024

J. Cancer

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Bicalutamide (BIC) resistance impedes the treatment of prostate cancer (PCa) and seems to involve ferroptosis; however, the underlying mechanism remains unclear. Our study aimed to explore how miR-15b-3p modulates ferroptosis in response to BIC resistance and determine whether the miRNA is suitable for early screening of PCa. Here, we found that PCa tissues had significantly higher miR-15b-3p expression than adjacent normal tissues. Analysis of blood samples in patients who underwent prostate-specific antigen (PSA) screening revealed that miR-15b-3p was a more accurate diagnostic than PSA (miR-15b-3p area under the curve [AUC] = 0.941, PSA AUC = 0.815). In vitro experiments then demonstrated that miR-15b-3p expression was markedly higher in LNCaP, PC-3, and DU145 cells than in RWPE-1 cells. Treatment with BIC decreased miR-15b-3p expression and progressive ferroptosis. Mechanistically, we identified KLF2 as the downstream target of miR-15b-3p. Overexpressing KLF2 facilitated ferroptosis via augmenting MDA and iron concentrations, in turn inhibiting the SLC7A11/GPX4 axis and decreasing GSH concentration. Through modulating ferroptosis, miR-15b-3p mimic and inhibitor weakened and enhanced BIC sensitivity, respectively. Furthermore, BIC treatment limited xenograft tumor volume in vivo, whereas agomir-15b-3p promoted tumor growth, indicating that miR-15b-3p attenuated the tumor-suppressive effects of BIC. Taken together, our results suggested that miR-15b-3p is crucial to BIC resistance, specifically via targeting KLF2 and thereby suppressing ferroptosis. High miR-15b-3p expression in early PCa screening should reflect a higher probability of cancer. In conclusion, miR-15b-3p has strong potential as a screening and diagnostic biomarker with reliable prospects for clinical application. Furthermore, because patients with high miR-15b-3p and low KLF2 expression have a greater risk of BIC resistance and malignant progression, targeting the miRNA and its downstream protein may be a new treatment strategy.

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Section: Discussionmentioning

confidence: 99%

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis

Zhang,

Yu,

Bai

et al. 2024

J. Cancer

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Expression and Clinical Significance of MiR-421 in Prostate Cancer

Huang,

He,

Zheng

et al. 2024

Biomarkers

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Androgen Signaling in Prostate Cancer: When a Friend Turns Foe

Pandey,

Sabharwal,

Tripathi

et al. 2025

EMIDDT

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Abstract:: Androgen (AR) signaling is the main signaling for the development of the prostate and its normal functioning. AR is highly specific for testosterone and dihydrotestosterone, significantly contributing to prostate development, physiology, and cancer. All these receptors have emerged as crucial therapeutic targets for PCa. In the year 1966, the Noble prize was awarded to Huggins and Hodge for their groundbreaking discovery of AR. As it is a pioneer transcription factor, it belongs to the steroid hormone receptor family and consists of domains, including DNA binding domain (DBD), hormone response elements (HRE), C-terminal ligand binding domain (LBD), and N-terminal regulatory domains. Structural variations in AR, such as AR gene amplification, LBD mutations, alternative splicing of exons, hypermethylation of AR, and co- regulators, are major contributors to PCa. It’s signaling is crucial for the development and functioning of the prostate gland, with the AR being the key player. The specificity of AR for testosterone and dihydrotestosterone is important in prostate physiology. However, when it is dysregulated, AR contributes significantly to PCa. However, the structural variations in AR, such as gene amplification, mutations, alternative splicing, and epigenetic modifications, drive the PCa progression. Therefore, understanding AR function and dysregulation is essential for developing effective therapeutic strategies. Thus, the aim of this review was to examine how AR was initially pivotal for prostate development and how it turned out to show both positive and detrimental implications for the prostate

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The role of miRNAin prostate cancer diagnosis, prognosisand treatment response: a narrative review

Cited by 4 publications

References 107 publications

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis

MiR-15b-3p weakens bicalutamide sensitivity in prostate cancer via targeting KLF2 to suppress ferroptosis

Expression and Clinical Significance of MiR-421 in Prostate Cancer

Androgen Signaling in Prostate Cancer: When a Friend Turns Foe

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