miR-1207-3p regulates the androgen receptor in prostate cancer via FNDC1/fibronectin

Abstract

Prostate cancer (PCa) is frequently diagnosed in men, and dysregulation of microRNAs is characteristic of many cancers. MicroRNA-1207-3p is encoded at the non-protein coding gene locus PVT1 on the 8q24 human chromosomal region, an established PCa susceptibility locus. However, the role of microRNA-1207-3p in PCa is unclear. We discovered that microRNA-1207-3p is significantly underexpressed in PCa cell lines in comparison to normal prostate epithelial cells. Increased expression of microRNA-1207-3p in PCa cells significantly inhibits proliferation, migration, and induces apoptosis via direct molecular targeting of FNDC1, a protein which contains a conserved protein domain of fibronectin (FN1). FNDC1, FN1, and the androgen receptor (AR) are significantly overexpressed in PCa cell lines and human PCa, and positively correlate with aggressive PCa. Prostate tumor FN1 expression in patients that experienced PCa-specific death is significantly higher than in patients that remained alive. Furthermore, FNDC1, FN1 and AR are concomitantly overexpressed in metastatic PCa. Consequently, these studies have revealed a novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in PCa.

A novel microRNA-1207-3p/FNDC1/FN1/AR regulatory pathway in prostate cancer

“…Prostate cancer (PCa) is the most commonly diagnosed male cancer in the western world [1,2] . With an estimated 22,800 newly diagnosed men in the US in 2015, PCa is a major cause of cancer morbidity and mortality [3] .…”

“…With an estimated 22,800 newly diagnosed men in the US in 2015, PCa is a major cause of cancer morbidity and mortality [3] . Although there has been progress made in the field, several areas of critical unmet needs remain in PCa, such as the molecular mechanisms underlying its development and progression [1,2,[4][5][6] . The complexity of the disease lies in its heterogeneity [1,2,7] .…”

“…Although there has been progress made in the field, several areas of critical unmet needs remain in PCa, such as the molecular mechanisms underlying its development and progression [1,2,[4][5][6] . The complexity of the disease lies in its heterogeneity [1,2,7] . The current tool for screening for PCa, prostate specific antigen (PSA), is highly controversial as it is not PCa-specific and has a high false positive rate [8,9] .…”

“…This poor correlation leads to adverse consequences associated with unnecessary diagnosis and overtreatment of non-aggressive PCa [8][9][10] . Currently, there are no biomarkers available that are effective for the early detection of PCa and sensitive enough to discriminate between indolent and aggressive PCa [1,11,12] . Therefore, the search continues for improved and reliable biomarkers which offer specificity, and improve risk RESEARCH HIGHLIGHT stratification and clinical outcomes for patients.…”

“…Public Health 2016, 13 (1) 12, have shown that the PVT1 gene locus, located on the 8q24 chromosomal locus, is dysregulated in PCa [21] . PVT1 has at least 12 different exons and encodes six microRNAs, including microRNA-1207-3p (miR-1207-3p) [1,5,21,24] . However, to the best of our knowledge, no study had been previously performed to determine the role and biological functions for miR-1207-3p in PCa.…”