miR-223-5p targeting ERG inhibits prostate cancer cell proliferation and migration

Abstract

Ectopic expression of miR-223-5p, the lagging strand of miR-223 duplex, has been reported acting as anti-tumor miRNA in many cancers. How miR-223-5p influencing prostate cancer (PCa) remains obscure and worth of experimental investigation. In this study, the expressions of miR-223-5p and ERG in common PCa cell lines were detected and compared to RWPE-1, respectively. Then luciferase reporter assay was performed to verify whether miR-223-5p could specifically target and regulate ERG. Further discovery ERG's role in the PCa oncogenesis was also conducted by up or down regulating miR-223-3p expression. We found miR-223-5p was significantly down-regulated in DU145, while it was only up-regulated in LNCaP. Similarly, ERG expression remarkably decreased in both PC-3 and DU145 than that in RWPE-1, but significantly increasing in LNCaP. Luciferase assay demonstrated slightly decreased ERG expression after miR-223-5p-mimics but significantly increased ERG expression after miR-223-5p-inhibtor. Using gene interference, we further confirmed that both ERG mRNA and protein expressions were decreased in all PCa lines transfected ERG siRNA, but increasing in both DU145 and LNCaP cells with miR-223-5p antisense oligonucleotides. MTT assay, Transwell invasion and migration assay supported the function of ERG in PCa oncogenesis. We revealed tumor suppressive abilities of miR-223-5p in PCa by negatively targeting ERG gene. It could serve as a fundamental supplement and extension of our previous study about miR-223-3p in PCa, revealing the coordinative regulation between miR-223-5p and miR-223-3p in PCa cell biological behaviors. Exploration of miR-233-duplex orientated pathway networks may help us develop novel potential therapeutic options for PCa.

CircGNG4 Promotes the Progression of Prostate Cancer by Sponging miR-223 to Enhance EYA3/c-myc Expression

“…miR-424 affects the ubiquitination and activation of STAT3 to promote prostate cancer development ( Dallavalle et al, 2016 ). In the present study, miR-233 was predicted to bind with circGNG4, and miR-223 has been determined to inhibit prostate cancer progression by targeting ETS transcription factor ERG (ERG) and integrin subunit α 3 (ITGA3)/integrin subunit β 1 (ITGB1) signaling ( Kurozumi et al, 2016 ; Wei et al, 2020 ). It is therefore hypothesized that circGNG4 exerts its oncogenic role via sponging miR-223, which blocks the anti-cancer effect of miR-233.…”

High-Throughput Sequencing Reveals the Differential MicroRNA Expression Profiles of Human Gastric Cancer SGC7901 Cell Xenograft Nude Mouse Models Treated with Traditional Chinese Medicine Si Jun Zi Tang Decoction

“…Dou et al [ 45 ] confirmed that miR-223-5p suppressed tumor growth and metastasis in non-small-cell lung cancer by targeting E2F8 (encoding E2F transcription factor 8). Recent research also showed that miR-223-5p targets ERG (encoding ETS transcription factor ERG) and inhibited prostate cancer cell proliferation and migration [ 46 ]. In addition, miR-205-5p expression in breast cancer tissues and cell lines was decreased compared with that in normal tissues and a normal cell line.…”

MicroRNA‑223‑5p suppresses the progression of nasopharyngeal carcinoma by targeting DCLK1

“…Numerous studies have revealed that miR-223-5p is significantly downregulated in cancer tissues and cells, suggesting its inhibitory effect on tumor progression. For example, miR-223-5p may inhibit the progression of non-small cell lung cancer by modulating E2F transcription factor 8 (8), suppress the malignant phenotype of prostate cancer cells via modulating ETS transcription factor ERG (9) and repress the aggressiveness of bladder cancer cells (10). However, the potential regulatory role of miR-223-5p in NPC has not been extensively investigated.…”