Orchestration of miRNA Patterns by Testosterone and Dietary Tomato Carotenoids during Early Prostate Carcinogenesis in TRAMP Mice

Authors

Lei Wan
Jennifer M Thomas-Ahner
Dennis K Pearl
John W Erdman
Nancy E Moran
Steven K Clinton

Publication Date

7-1-2023

Journal

The Journal of Nutrition

DOI

10.1016/j.tjnut.2023.05.015

PMID

37187350

PMCID

PMC10375503

PubMedCentral® Posted Date

5-13-2023

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Humans, Male, Mice, Animals, Carotenoids, Lycopene, Testosterone, Prostate, Solanum lycopersicum, Androgens, MicroRNAs, Prostatic Neoplasms, Carcinogenesis, Diet, Mice, Transgenic, tomato, lycopene, miRNA, prostate cancer, testosterone

Abstract

Background: The integrative effects of prostate cancer risk factors, such as diet and endocrine status, on cancer-associated miRNA expression are poorly defined.

Objectives: This study aimed to define the influence of androgens and diet (tomato and lycopene) on prostatic miRNA expression during early carcinogenesis in the transgenic adenocarcinoma of the mouse prostate (TRAMP) model.

Methods: Wild type (WT) and TRAMP mice were fed control, tomato-containing, or lycopene-containing diets from 4 to 10 weeks of age. Mice underwent either sham (intact) or castration surgery at 8 wk, and half of the castrated mice received testosterone (2.5 mg/kg body weight/d) at 9 wk. Mice were killed at 10 wk, and dorsolateral prostate expression of 602 miRNAs was assessed.

Results: We detected expression of 88 miRNAs (15% of 602), all of which were present in the TRAMP, in comparison with 49 miRNAs being detectable (8%) in WT. Expression of 61 miRNAs differed by TRAMP genotype, with the majority upregulated in TRAMP. Of the 61 miRNAs, 42 were responsive to androgen status. Diet affected 41% of the miRNAs, which differed by genotype (25/61) and 48% of the androgen-sensitive miRNAs (20/42), indicating overlapping genetic and dietary influences on prostate miRNAs. Tomato and lycopene feeding influenced miRNAs previously associated with the regulation of androgen (miR-145 and let-7), MAPK (miR-106a, 204, 145/143, and 200b/c), and p53 signaling (miR-125 and miR-98) pathways.

Conclusions: Expression of miRNAs in early prostate carcinogenesis is sensitive to genetic, endocrine, and diet drivers, suggesting novel mechanisms by which tomato and lycopene feeding modulate early prostate carcinogenesis.