MicroRNA-302a Suppresses Tumor Cell Proliferation by Inhibiting AKT in Prostate Cancer

Abstract

Micro (mi) RNAs are important regulators involved in various physical and pathological processes, including cancer. The miRNA-302 family has been documented as playing a critical role in carcinogenesis. In this study, we investigated the role of miRNA-302a in prostate cancer (PCa). MiRNA-302a expression was detected in 44 PCa tissues and 10 normal prostate tissues, and their clinicopathological significance was analyzed. Cell proliferation and cell cycle analysis were performed on PCa cells that stably expressed miRNA-302a. The target gene of miRNA-302a and the downstream pathway were further investigated. Compared with normal prostate tissues, miRNA-302a expression was downregulated in PCa tissues, and was even lower in PCa tissues with a Gleason score ≥8. Overexpression of miRNA-302a induced G1/S cell cycle arrest in PCa cells, and suppressed PCa cell proliferation both in vitro and in vivo. Furthermore, miRNA-302a inhibits AKT expression by directly binding to its 3΄ untranslated region, resulting in subsequent alterations of the AKT-GSK3β-cyclin D1 and AKT-p27Kip1 pathway. These results reveal miRNA-302a as a tumor suppressor in PCa, suggesting that miRNA-302a may be used as a potential target for therapeutic intervention in PCa.

Application of the microRNA‐302/367 cluster in cancer therapy

“…In addition, upregulation of the miR‐302/367 cluster in PCa has protumorigenic effects in vivo and in vitro through enhanced cell proliferation, sphere formation, and migration through the miR‐302/367/LATS2/YAP pathway . However, in another PCa study, miR‐302a functioned as a tumor suppressor by influencing the AKT‐GSK‐3β‐CCND1 and AKT‐p27Kip1 pathways . The second PCa study did not verify the conclusions in animal models, and the clinical sample size was not large enough.…”

Gene interference strategies as a new tool for the treatment of prostate cancer

“…Furthermore, miRNA-302a inhibits AKT expression through a binding with its 3 0 untranslated region, and alterations of the AKT/GSK3b-cyclin D1 and AKT-p27Kip1 pathway. These results reveal miRNA-302a as a tumor suppressor in PCa, and that it may be useful in a new therapeutic strategy in PCa [131]. Other important markers which could be potential therapeutic targets in PCa are a group of 12 miRNAs that bind the 3c-untranslated region of Bmi-1 mRNA in PC-3 cells.…”

miR302a inhibits the proliferation of esophageal cancer cells through the MAPK and PI3K/Akt signaling pathways

“…Furthermore, total Akt and ERK1/2 expression levels were also determined by western blot analysis in TE-10 and ECA109 cells, and overexpression of miR302a did not markedly differ between groups. miR302a overexpression has been demonstrated to significantly inhibit cell proliferation by inhibiting Akt in colon cancer and prostate cancer (10,27). Furthermore, miR-302 has also been reported to inhibit cancer cell proliferation via the Akt signaling pathway, and the microRNA-302-367 cluster suppressed the proliferation of cervical carcinoma cells through the novel target Akt1 (28).…”

“…Guo et al (9) demonstrated that miR302a is involved in the inhibition of ovarian cancer cell proliferation, and enhances cell apoptosis through targeting syndecan 1. In addition, miR302a suppresses tumor cell proliferation by inhibiting protein kinase B (AKT) in prostate cancer (10). However, miR302a expression and its involvement in esophageal cancer remain undetermined, and the underlying mechanisms of miR302a in esophageal cancer cells remain unknown.…”