miR‐15b‐5p facilitates the tumorigenicity by targeting RECK and predicts tumour recurrence in prostate cancer

Abstract

MicroRNAs (miRNAs) have been reported to participate in many biological behaviours of multiple malignancies. Recent studies have shown that miR‐15b‐5p (miR‐15b) exhibits dual roles by accelerating or blocking tumour progression. However, the molecular mechanisms by which miR‐15b contributes to prostate cancer (PCa) are still elusive. Here, miR‐15b expression was found significantly up‐regulated in PCa in comparison with the normal samples and was positively correlated with age and Gleason score in patients with PCa. Notably, PCa patients with miR‐15b high expression displayed a higher recurrence rate than those with miR‐15b low expression (P = 0.0058). Knockdown of miR‐15b suppressed cell growth and invasiveness in 22RV1 and PC3 cells, while overexpression of miR‐15b reversed these effects. Then, we validated that RECK acted as a direct target of miR‐15b by dual‐luciferase assay and revealed the negative correlation of RECK with miR‐15b expression in PCa tissues. Ectopic expression of RECK reduced cell proliferation and invasive potential and partially abrogated the tumour‐promoting effects caused by miR‐15b overexpression. Additionally, miR‐15b knockdown inhibited tumour growth activity in a mouse PCa xenograft model. Taken together, our findings indicate that miR‐15b promotes the progression of PCa cells by targeting RECK and represents a potential marker for patients with PCa.

Long noncoding RNA LINC00662‐miR‐15b‐5p mediated GPR120 dysregulation contributes to osteoarthritis

“…Consistent with these findings, the present study demonstrated that GPR120 plays a critical role in the development of OA. Studies show that miR‐15b‐5p exhibits dual roles by accelerating or blocking tumor progression . Importantly, a recent study shows that miR‐15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting insulin‐like growth factor 1 (IGF1), IGF1 receptor (IGF1R) and B‐cell CLL/lymphoma 2 (BCL2) …”

MiR-15b is a key regulator of proliferation and apoptosis of chondrocytes from patients with condylar hyperplasia by targeting IGF1, IGF1R and BCL2

“…The other reasonable explanation is that caspase 3 could be positively affected by certain genes which are targeted by miR-15b. Indeed, enhanced expression of miR-15b in a prostate cancer cell line inhibited reversion-inducing cysteine-rich protein with Kazal motifs (RECK) signal activation, thereby leading to caspase 3 reduction 38 .…”

Long Non-Coding RNA MAGI2-AS3 is a New Player with a Tumor Suppressive Role in High Grade Serous Ovarian Carcinoma

“…Investigating along these lines, MAGI2-AS3 has been experimentally demonstrated to regulate the expression of three miRNAs-miR-15b-5p, miR-374a-5p, and miR-374b-5p that were previously associated with this lncRNA in other cancers [31][32][33]. It is indeed interesting to note that these three miRNAs that are upregulated in EOC [36] have been reported to have oncogenic roles in several other cancers [38,40,41,[49][50][51][52][53][54][55][56][57][58]. It should be mentioned that some miRNAs, for example miR-15b-5p, have been observed to have conflicting roles as both oncogenes and tumor suppressors [49,50,59].…”

“…miRNAs check the expression of specific proteins by complementary binding to their mRNA transcripts and cause their degradation [17]. Therefore, to further expand the ceRNA network of MAGI2-AS3, four mRNAs-HOXA5, MTSS1, PTEN, and RECK, reported to be associated with at least one of these three miRNAs-miR-15b-5p, miR-374a-5p, and miR-374b-5p (shown in Supplementary Materials Table S4) [37][38][39][40][41] and having oncosuppressive functions in OC [42][43][44][45] were selected. To determine their involvement in MAGI2-AS3 ceRNA network, the co-expression pattern of MAGI2-AS3 with each of the four mRNAs (HOXA5, MTSS1, PTEN, and RECK) in both OC (TCGA-OV) and FT (GTEx) was examined, as shown in Supplementary Materials Figure S2.…”