MicroRNA-375 plays a dual role in prostate carcinogenesis

Abstract

BackgroundProstate cancer (PCa), a highly incident and heterogeneous malignancy, mostly affects men from developed countries. Increased knowledge of the biological mechanisms underlying PCa onset and progression are critical for improved clinical management. MicroRNAs (miRNAs) deregulation is common in human cancers, and understanding how it impacts in PCa is of major importance. MiRNAs are mostly downregulated in cancer, although some are overexpressed, playing a critical role in tumor initiation and progression. We aimed to identify miRNAs overexpressed in PCa and subsequently determine its impact in tumorigenesis.ResultsMicroRNA expression profiling in primary PCa and morphological normal prostate (MNPT) tissues identified 17 miRNAs significantly overexpressed in PCa. Expression of three miRNAs, not previously associated with PCa, was subsequently assessed in large independent sets of primary tumors, in which miR-182 and miR-375 were validated, but not miR-32. Significantly higher expression levels of miR-375 were depicted in patients with higher Gleason score and more advanced pathological stage, as well as with regional lymph nodes metastases. Forced expression of miR-375 in PC-3 cells, which display the lowest miR-375 levels among PCa cell lines, increased apoptosis and reduced invasion ability and cell viability. Intriguingly, in 22Rv1 cells, which displayed the highest miR-375 expression, knockdown experiments also attenuated the malignant phenotype. Gene ontology analysis implicated miR-375 in several key pathways deregulated in PCa, including cell cycle and cell differentiation. Moreover, CCND2 was identified as putative miR-375 target in PCa, confirmed by luciferase assay.ConclusionsA dual role for miR-375 in prostate cancer progression is suggested, highlighting the importance of cellular context on microRNA targeting.Electronic supplementary materialThe online version of this article (doi:10.1186/s13148-015-0076-2) contains supplementary material, which is available to authorized users.

MicroRNA-375 targets PAX6 and inhibits the viability, migration and invasion of human breast cancer MCF-7 cells

“…Deregulated miR-375 has been identified in numerous cancer types, including laryngeal squamous cell carcinoma (23), head and neck squamous cell carcinoma (24), prostate cancer (25), hepatocellular carcinoma (26), lung cancer (27) and breast cancer (28). Wu et al (29) examined the circulating miR profile in patients with breast cancer by deep sequencing all circulating small RNAs.…”

Low folate levels are associated with methylation-mediated transcriptional repression of miR-203 and miR-375 during cervical carcinogenesis

“…Alhough miR-375 has primarily been studied in the context of diabetes, as it influences β-cell mass and insulin levels, its expression has also been demonstrated to be decreased in several malignancies (33). Wang et al (34) used stem-loop RT-qPCR to detect the expression levels of miR-375 in cervical cancer tissues (170 cases) and normal cervical tissues (68 cases).…”

The Role of the Clinical and Molecular Assays in Prostate Cancer Detection

“…Using current the public database miRBase, 2500 mature miRNA have been discovered. They are ideal candidates for innovating new early detection and diagnosis for cancer [1,34,35]. A miRNAs are a group of small noncoding RNA molecules that are transcribed by polymerase II to producing the primary miRNA (pre-miRNA).…”

“…Prostate cancer is the second type of cancer in men (aged 65-79 years) [1]. In fact, about 60% of all prostate cancers are diagnosed in men over the age of 66 years, and 97% are diagnosed in men at 50 years.…”