Russo Valentina, Tamburrino Lara, Morselli Simone, Sani Cristina, Baldi Elisabetta, Sebastianelli Arcangelo, Raspollini Maria Rosaria, Mongia Alessandra, Carradori Valentina, Lallo Eleonora, Munnia Armelle, Bisanzi Simonetta, Marchiani Sara, Visioli Carmen, Rapi Stefano, Serni Sergio, Zappa Marco, Carozzi Francesca, Peluso Marco
Regional Laboratory of Cancer Prevention, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), 50139, Florence, Italy.
Andrology, Women's Endocrinology and Gender Incongruence Unit, Center for Prevention, Diagnosis and Treatment of Infertility, Careggi University Hospital, 50139, Florence, Italy.
Prostate Cancer Prostatic Dis. 2025 Mar;28(1):202-209. doi: 10.1038/s41391-024-00809-z. Epub 2024 Feb 24.
Hyperglycemia can promote the development of prostate cancer (PCa). Differential expression levels of miRNAs between PCa patients and controls were also reported. Therefore, we examined the relationship between hyperglycemia and miRNA levels in PCa.
Relative expression of urinary miR-574-3p, miR-375, miR-205-5p, miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p were investigated in 105 PCa patients and 138 noncancer controls by Real-Time quantitative PCR. Fasting plasma glucose measurements were retrieved from clinical records. The differential miRNA expressions among groups were compared using non-parametric tests. Correlations with glucose and prostate-specific antigen (PSA) were tested using Pearson correlation coefficient.
When we analyzed miRNA expression according to glycemic state, significant down-regulations were found for miR-200b-3p, miR-187-3p, miR-182-5p, and miR-100-5p in noncancer controls with high glucose. The lowest down-regulations were observed for miR-187-3p, miR-182-5p, and miR-100-5p. Subsequently, when hyperglycemia was considered in PCa, significant dysregulations of selected miRNAs were found in hyperglycemic PCa patients than in controls with high glucose. In particular, miR-375 and miR-182-5p showed a 3-FC in hyperglycemic PCa patients than controls who left hyperglycemia untreated. Conversely, only a down-regulation of miR-574-3p was observed in PCa patients regardless of glycemic status and only modest down-regulation of miR-574-3p, miR-200b-3p, miR-187-3p and miR-182-5p were found in normoglycemic PCa patients. Next, significant correlations between miRNAs and glucose (miR-200b-3p, miR-100-5p) and PSA (miR-205-5p and miR-187-3p) were detected in controls. Similarly, miR-205-5p and miR-187-3p were correlated with glucose in PCa patients, while miR-574-3p and miR-375 showed inverse relationships.
miRNA dysregulations can occur in hyperglycemic PCa patients as compared to noncancer controls who left hyperglycemia untreated. Hyperglycemia can consistently promote the expression of miR-375 and miR-182-5p. Uncontrolled hyperglycemic state could contribute to the creation of a suitable microenvironment for later PCa development by promoting gene expression.
高血糖可促进前列腺癌（PCa）的发展。也有报道称PCa患者与对照组之间miRNA的表达水平存在差异。因此，我们研究了PCa中高血糖与miRNA水平之间的关系。
通过实时定量PCR检测了105例PCa患者和138例非癌对照者尿液中miR-574-3p、miR-375、miR-205-5p、miR-200b-3p、miR-187-3p、miR-182-5p和miR-100-5p的相对表达。从临床记录中获取空腹血糖测量值。使用非参数检验比较各组间miRNA表达的差异。使用Pearson相关系数检验与血糖和前列腺特异性抗原（PSA）的相关性。
当我们根据血糖状态分析miRNA表达时，发现高血糖的非癌对照者中miR-200b-3p、miR-187-3p、miR-182-5p和miR-100-5p有显著下调。miR-187-3p、miR-182-5p和miR-100-5p的下调程度最低。随后，在PCa中考虑高血糖时，发现高血糖PCa患者中所选miRNA的失调比未治疗高血糖的对照者更显著。特别是，与未治疗高血糖的对照者相比，高血糖PCa患者中miR-375和miR-182-5p显示出3倍变化（3-FC）。相反，无论血糖状态如何，PCa患者中仅观察到miR-574-3p下调，而在血糖正常的PCa患者中仅发现miR-574-3p、miR-200b-3p、miR-187-3p和miR-182-5p有适度下调。接下来，在对照者中检测到miRNA与血糖（miR-200b-3p、miR-100-5p）和PSA（miR-205-5p和miR-187-3p）之间存在显著相关性。同样，在PCa患者中miR-205-5p和miR-187-3p与血糖相关，而miR-574-3p和miR-375呈负相关。
与未治疗高血糖的非癌对照者相比，高血糖PCa患者中可能发生miRNA失调。高血糖可持续促进miR-375和miR-182-5p的表达。不受控制的高血糖状态可能通过促进基因表达为后期PCa的发展创造适宜的微环境。
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