Ovarian cancer is a leading cause of cancer death as diagnosis is frequently delayed to an advanced stage. leading cause of death among women in developed countries. If diagnosed at stage I with the malignancy confined to the ovary, the 5-year survival rates can reach up to 94%. However, survival rates sharply decline to 28% for advanced stages at presentation.1 Insufficient biomarker(s) and the lack of an effective screening strategy for early detection result in >80% of patients presenting with advanced disease at the time of diagnosis. Serum marker CA125 (cancer antigen 125) is usually clinically used in ovarian cancer screening, but it lacks the sensitivity and specificity to function independently in a test.2 A sensitive biomarker for accurate early detection of ovarian cancer is urgently needed. Prostasin (protease serine 8 or PRSS8) is usually a trypsin-like serine peptidase expressed in epithelial cells and is usually found as GR 38032F a cell surface bound or secreted protein. Prostasin is usually altered in ovarian, prostate, breast and gastric cancers3, 4, 5, 6 and has been proposed to inhibit cancer cell proliferation and invasion upon activation.7 In particular, prostasin is overexpressed in ovarian cancer and may serve as a potential biomarker for early detection of ovarian cancer independently or in combination with CA125.4, 8, 9 Prostatic secretory protein 94 (PSP94) also termed microseminoprotein beta (MSMB) is the second most abundant protein in the semen of healthy men and is found in a variety of human tissues.10, 11, 12 The cellular levels of PSP94 gradually decreases with the progression of prostate GR 38032F cancer, suggesting that PSP94 may represent a promising target for cancer treatment and a potential biomarker for early detection of prostate cancer.13 In addition, genome-wide association studies and functional analysis of underlying MSMB gene correlate with polymorphism of the gene promoter region, resulting in altered MSMB expression with prostate cancer GR 38032F risk.14, 15, 16, GR 38032F 17 MicroRNAs (miRNAs) regulate gene expression at posttranscriptional level in diversely biological functions such as cell proliferation, differentiation and apoptosis.18, 19 The Let-7 family of miRNAs consists of more than 10 sequence-conserved members with similar functions across diverse species from worms to humans.20 Deregulation of Let-7 has been linked to many types of cancer and other diseases.20, 21 An RNA-binding protein termed Lin28b was recently identified as a direct upstream inhibitor of Let-7 family signaling22, 23 with important functions in embryonic stem cells and embryonal carcinoma cells.24, 25, 26, 27 Balanced signaling of Lin28b to Let-7 is critical; imbalance is usually linked to various diseases.28 Our recent studies demonstrated important roles and functional similarity of prostasin and PSP94 in ovarian cancer chemoresistance.29, 30 In the current study, we report that Rabbit Polyclonal to TCF7L1 prostasin expression is regulated by PSP94 and shares all examined downstream targets with PSP94 in ovarian cancer cells. PSP94 and prostasin are both overexpressed in strong correlation with Lin28b/Let-7 expression levels in tissues of GR 38032F ovarian cancer patients. As a result, PSP94 and the PSP94/prostasin axis may represent promising markers for early detection of ovarian cancer as well as potential therapeutic targets. This role may be extended to other types of cancers where either one or both components are altered. Results PSP94 regulates prostasin expression in ovarian cancer cells PSP94 and prostasin both play important roles in chemoresistance and share.