MiR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A

Abstract

Deregulation of microRNAs contributes to the abnormal cell growth which is frequently observed in cancer. In the current study, we detected the expression and regulatory relationship between miR‐10a and Lysine‐specific demethylase 4A (KDM4A) to reveal their function in prostate cancer (PCa) progression. We found that miR‐10a levels were significantly decreased in PCa cell lines in comparison with the normal epithelial cell line RWPE‐1. Downregulation of miR‐10a levels was also observed in tumor tissues from PCa patients compared with the adjacent normal tissues. Enhanced expression of miR‐10a inhibited cell proliferation and colony forming capability of PCa cells. In addition, quantitative real‐time polymerase chain reaction and Western blot analysis showed a significant decrease of KDM4A in response to miR‐10a elevation in PCa cells. Using dual luciferase assay, we confirmed that KDM4A was a target gene for miR‐10a. Furthermore, Western blot analysis indicated that miR‐10a overexpression inactivated YAP signaling and suppressed transcription of YAP target genes. Additionally, cell growth arrest and colony forming capacity inhibition induced by miR‐10a overexpression could be reversed by YAP overexpression in PCa cells. More importantly, miR‐10a mimics inhibited PC‐3 tumor growth in nude mice accompanied with a remarkable reduction of KDM4A and YAP expression. In conclusion, our results uncovered a tumor suppressor role of miR‐10a in PCa via negative regulation of KDM4A and its downstream Hippo‐YAP pathway.

RETRACTED: Targeting USP1‐dependent KDM4A protein stability as a potential prostate cancer therapy

“…However, it should be noted that 25.5% (26 of 102) of all tumor specimens had high KDM4A expression but low USP1 expression (Figure 6D). Taken together, these results reveal that upregulation of USP1 expression could contribute to KDM4A overexpression in a substantial fraction of human prostate tumors, whereas in other prostate tumors, KDM4A can be activated by other posttranslational regulation, eg downregulation of microRNA‐10 was correlated with high expression levels of KMD4A in human prostate tumors 29 …”

High-Throughput and Automated Acoustic Trapping of Extracellular Vesicles to Identify microRNAs With Diagnostic Potential for Prostate Cancer

“…Our analysis of each differentially expressed miRNA in the cohort revealed that eight miRNAs likely arise as a result of false positive, driven by low number of reads in a limited number of samples while six are robust and not affected by any similar flaws. Published literature revealed that four of the six curated miRNAs, miR-1, miR-23b, miR-27a, and miR-27b, function as putative tumor suppressors that modulate proliferation and epithelial-mesenchymal transition in prostate and bladder cancer (30)(31)(32)(33)(34)(35)(36). The result portrays a mechanism that is consistent with literature in which tumor suppressor miRNAs are down-regulated during PCa progression (37).…”

Tumor‐suppressive microRNA‐10a inhibits cell proliferation and metastasis by targeting Tiam1 in esophageal squamous cell carcinoma

“…Moreover, microRNA‐10a was reported to be in involved in the metastatic process by regulating EMT and hepatoma cell adhesion . In addition, miR‐10a functions as a tumor suppressor in prostate cancer via targeting KDM4A . Furthermore, miR‐10a could inhibit cell proliferation and promote cell apoptosis by targeting BCL6 in diffuse large B‐cell lymphoma …”