MiR-19b-3p and miR-101-3p as potential biomarkers for prostate cancer diagnosis and prognosis

被引:5
作者
Duca, Rocio B. [1 ]
Massillo, Cintia [1 ]
Dalton, Guillermo N. [1 ]
Farre, Paula L. [1 ]
Grana, Karen D. [1 ]
Gardner, Kevin [2 ]
De Siervi, Adriana [1 ]
机构
[1] Consejo Nacl Invest Cient & Tecn, Inst Biol & Med Expt IBYME, Lab Oncol Mol & Nuevos Blancos Terapeut, Buenos Aires, DF, Argentina
[2] Columbia Univ, Med Ctr, Dept Pathol & Cell Biol, 630 W 168th St, New York, NY 10032 USA
来源
AMERICAN JOURNAL OF CANCER RESEARCH | 2021年 / 11卷 / 06期
关键词
High fat diet; prostate cancer; miR-19b-3p; miR-101-3p; biomarker; METABOLIC SYNDROME; CELL-MIGRATION; METASTASIS; ADHESION; RISK; EXPRESSION; APOPTOSIS; INTEGRIN; INVASION; INSULIN;
D O I
暂无
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Prostate cancer (PCa) is the most commonly diagnosed male malignancy worldwide. Early diagnosis and metastases detection are crucial features to diminish patient mortality. High fat diet (HFD) and metabolic syndrome increase PCa risk and aggressiveness. Our goal was to identify miRNAs-based biomarkers for PCa diagnosis and prognosis associated with HFD. Mice chronically fed with a HFD or control diet (CD) were subcutaneously inoculated with androgen insensitive PC3 cells. Xenografts from HFD-fed mice showed increased expression of 7 miRNAs that we named "candidates" compared to CD-fed mice. These miRNAs modulate specific metabolic and cancer related pathways. Using bioinformatic tools and human datasets we found that hsa-miR-19b-3p and miR-101-3p showed more than 1,100 validated targets involved in proteoglycans in cancer and fatty acid biosynthesis. These miRNAs were significantly increased in the bloodstream of PCa patients compared to non-PCa volunteers, and in prostate tumors compared to normal adjacent tissues (NAT). Interestingly, both miRNAs were also increased in tumors of metastatic patients compared to tumors of non-metastatic patients. Further receiver-operating characteristic (ROC) analysis determined that hsa-miR-19b-3p and hsa-miR-101-3p in serum showed poor predictive power to discriminate PCa from non-PCa patients. Hsa-miR-19b-3p showed the best score to discriminate between tumor and NAT, while hsa-miR-101-3p was useful to differentiate between metastatic and non-metastatic PCa patients. Hsa-miR101-3p was increased in exosomes isolated from blood of PCa patients. Although more detailed functional exploration and validation of the molecular mechanisms are required, we identified hsa-miR-19b-3p and hsa-miR-101-3p with high potential for PCa diagnosis and prognosis.
引用
收藏
页码:2802 / 2820
页数:19
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