The role of single nucleotide polymorphisms of miRNAs 100 and 146a as prognostic factors for prostate cancer

Camargo, Juliana Alves de; Lopes, Renan Eboli; Ferreira, Gabriel Fernandes Dias; Viana, Nayara; Guimarães, Vanessa Valente; Leite, Kátia Ramos Moreira; Nahas, William C.; Srougi, Miguel; Antunes, Alberto A.; Reis, Sabrina T.

doi:10.1177/1724600821997461

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…The dysregulation of the expression of a miRNA can be due to mutations in its coding genes or in their regulatory regions; for example, SNPs in miR-146a and in miR-100 have been identified that act as a factor of bad and an improved prognosis in PCa. In addition, it has been mentioned that these polymorphisms could alter miRNA function ( 19 ). Furthermore, it has been observed that mutations can affect the biogenesis of the mature miRNA while it is in the ‘seed’ region of the passenger strand, thus decreasing its expression ( 20 , 21 ).…”

Section: Discussionmentioning

confidence: 99%

Deletion in a regulatory region is associated with underexpression of miR-148b‑3p in patients with prostate cancer

Bergez‑Hernández,

Luque‑Ortega,

García‑Magallanes

et al. 2024

Biomed Rep

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Prostate cancer (PCa) is the leading cause of cancer-related death in men. This pathology is complex and heterogeneous; therefore, elucidating the molecular mechanisms that lead to its origin and progression is imperative. MicroRNAs (miRNAs or miRs) are part of the epigenetic machinery that regulates the expression of human genes, therefore, mutations in the genes that encode them can lead to a dysregulation in their expression, which directly impacts their target genes, which could be oncogenes or tumor suppressor genes. In PCa several dysregulated expression levels of miRNAs are associated with perturbed cellular processes. A differential expression of miRNAs such as miR-145-5p and miR-148-3p has been observed in PCa, possibly due to mutations in regions near the miRNAs. However, the molecular mechanisms that lead to the dysregulation of these miRNAs still need to be clarified. Therefore, the present study aimed to analyze the expression of miRNAs and their relationship with mutations in patients with and without PCa. In total, 71 patients were analyzed: 41 of whom had PCa (CAP group) and 30 with benign pathology (BPD group). Underexpression was observed in miR-145-5p and miR-148b-3p in PCa patients (P=0.03 and P=0.001, respectively). In miR-145-5p, no mutations related to its expression were identified. For miR-148b-3p, a set of mutations were identified in the chr12:54337042/54337043 region, which were grouped into the mutation named DelsAAG. Although this mutation's abnormal allele is related to PCa (P=0.017), a statistically significant difference was observed in the expression of miR-148b-3p between carriers and non-carriers of the mutated allele, identifying a mechanism likely to be involved in the miR-148b-3p dysregulation.

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Section: Discussionmentioning

confidence: 99%

Deletion in a regulatory region is associated with underexpression of miR-148b‑3p in patients with prostate cancer

Bergez‑Hernández,

Luque‑Ortega,

García‑Magallanes

et al. 2024

Biomed Rep

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“…In recent decades, there has been considerable interest in the potential clinical value of miRNAs in PCa [18], especially by our research group [19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Eedunuri et al (2015) [7] showed that miR-137 negatively regulates the three genes comprising the p160 family.…”

Section: Discussionmentioning

confidence: 99%

Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer

Pimenta

Mioshi

Gonçalves

et al. 2023

IJMS

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MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 μg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals’ serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

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“…In recent years, numerous studies have investigated the associations between SNPs in miRNA genes and the risks of various types of cancer [25][26][27][28][29][30]. Although conflicting and inconsistent results have been obtained, the differences in association among studies may be due to different dietary habits, environmental exposures, and most importantly, different genetic background among the various study populations.…”

Section: Discussionmentioning

confidence: 99%

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan

Wang,

Chang,

Liao

et al. 2023

Biomedicines

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The aim of this study was to investigate the association between single-nucleotide polymorphisms (SNPs) in mir146a and mir196a and bladder cancer (BLCA) risk in Taiwan. The genotypes of mir146a rs2910164 and mir196a rs11614913 were determined in 375 BLCA patients and 375 healthy controls using PCR-RFLP methodology, and their associations with BLCA risk were evaluated. The study also measured the serum expression level of mir146a using quantitative RT-PCR. The results showed that the distributions of CC, CG and GG genotypes of mir146a rs2910164 were 31.7%, 45.6% and 22.7% in the control group, and 21.9%, 44.3% and 33.8% in the case group, respectively. In logistic regression analyses, the heterozygous variant genotype CG carriers showed a marginally significant association with increased BLCA risk (OR = 1.41, 95% CI = 0.99–2.01), while the homozygous variant genotype GG carriers had a 2.17-fold increased risk of BLCA (OR = 2.17, 95%CI = 1.46–3.21). Moreover, carriers of the GG/CG genotypes had significantly higher serum levels of mir146a than those with the CC genotype (p < 0.0001), indicating a genotype–phenotype correlation. In contrast, mir196a rs11614913 was not associated with BLCA risk. Therefore, the genotypes of mir146a rs2910164 may serve as a useful biomarker for predicting the risk of BLCA.

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The role of single nucleotide polymorphisms of miRNAs 100 and 146a as prognostic factors for prostate cancer

Cited by 5 publications

References 27 publications

Deletion in a regulatory region is associated with underexpression of miR-148b‑3p in patients with prostate cancer

Deletion in a regulatory region is associated with underexpression of miR-148b‑3p in patients with prostate cancer

Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer

Impacts of Mir146a Genotypes on Bladder Cancer Risk in Taiwan

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