miR-539 inhibits prostate cancer progression by directly targeting SPAG5

Abstract

BackgroundWe conducted multiple microarray datasets analyses from clinical and xenograft tumor tissues to search for disease progression-driving oncogenes in prostate cancer (PCa). Sperm-associated antigen 5 (SPAG5) attracted our attention. SPAG5 was recently identified as an oncogene participating in lung cancer and cervical cancer progression. However, the roles of SPAG5 in PCa progression remain unknown.MethodsSPAG5 expression level in clinical primary PCa, metastatic PCa, castration resistant PCa, neuroendocrine PCa, and normal prostate tissues was investigated. We established multiple in vivo xenografts models using patient-derived tissues and investigated SPAG5 expression trend in these models. We also investigated the functions of SPAG5 in vivo and in vitro studies. Luciferase reporter assays were performed to investigate potential miRNAs that can regulate SPAG5.ResultsWe identified that SPAG5 expression was gradually increased in PCa progression and its level was significantly associated with lymph node metastasis, clinical stage, Gleason score, and biochemical recurrence. Our results indicated that SPAG5 knockdown can drastically inhibit PCa cell proliferation, migration, and invasion in vitro and supress tumor growth and metastasis in vivo. We identified that miR-539 can directly target SPAG5. Ectopic overexpression of miR-539 can drastically inhibit SPAG5 expression and the restoration of SPAG5 expression can reverse the inhibitory effects of miR-539 on PCa cell proliferation and metastasis.ConclusionOur results collectively showed a progression-driving role of SPAG5 in PCa which can be regulated by miR-539, suggesting that miR-539/SPAG5 can serve as a potential therapeutic target for PCa.Electronic supplementary materialThe online version of this article (doi:10.1186/s13046-016-0337-8) contains supplementary material, which is available to authorized users.

MicroRNA‑539 inhibits colorectal cancer progression by directly targeting SOX4

“…Gu et al (39) reported that miR-539 expression is decreased in thyroid cancer tissues and cell lines. In addition, consistent with these results, low expression levels of miR-539 was observed in nasopharyngeal carcinoma (21) and prostate cancer (20). The high frequency of miR-539 downregulation in these types of human cancer suggested that miR-539 may be a novel marker for the diagnosis and prognosis of specific cancers.…”

“…To date, few genes have been validated as direct targets of miR-539, including sperm associated antigen 5 in prostate cancer (20), cyclin dependent kinase 4 in nasopharyngeal carcinoma (21), matrix metalloproteinase 8 in osteosarcoma (22) and caspase recruitment domain family member 11 in thyroid cancer (39). In the present study, SOX4 was validated as a novel direct and functional target of miR-539 in CRC.…”

“…Lv et al (21) reported that enforced expression of miR-539 suppresses the growth of nasopharyngeal carcinoma cells in vitro and in vivo. Meanwhile, Zhang et al (20) demonstrated that restoration of miR-539 expression in prostate cancer represses cell proliferation, migration and invasion in vitro, and decreases tumor growth and metastasis in vivo. These results suggest that miR-539 may serve an important function in these types of cancer, and it may be a potential target for the treatment of specific cancers.…”

“…miR-539 has been reported to be aberrantly expressed in several types of cancer including prostate cancer (20), nasopharyngeal carcinoma (21) and osteosarcoma (22). However, the expression levels, biological functions and underlying mechanisms of miR-539 in CRC remain unclear.…”

High expression of SPAG5 sustains the malignant growth and invasion of breast cancer cells through the activation of Wnt/β‐catenin signalling

“…Notably, SPAG5 has been shown to promote the proliferation, migration and invasion of various cancer cells. Inhibition of SPAG5 reduces the growth of prostate cancer cells in vitro and in vivo . SPAG5 overexpression promotes the proliferation and reduces the apoptosis of bladder urothelial carcinoma cells .…”