MicroRNA-744 promotes prostate cancer progression through aberrantly activating Wnt/β-catenin signaling

Abstract

Accumulated evidence indicate that miR-744 functions as either tumor suppressor or oncogene in the progression of a variety of tumors, with a tumor type-specific way. However, little is known about how miR-744 impacts on the tumorigenesis of human prostate cancer. In this study, employing the analyses of microarray, qRT-PCR and re-analysis of MSKCC data, we found that CRPC tissues expressed much more miR-744 than ADPC tissues did, and the expression level of miR-744 was inversely associated with survival of CRPC patients. In vitro studies revealed that miR-744 promotes PCa cells proliferation, enhances migration, invasion; in vivo results demonstrated that silencing of miR-744 mediated by shRNA dramatically reduces PCa xenograft tumor growth. Importantly, through human gene expression array, pathway enrichment analysis and Western blot, we identified that miR-744 dramatically activated Wnt/β-catenin pathway by targeting multiple negative regulators of Wnt/β-catenin signaling, including SFRP1, GSK3β, TLE3 and NKD1. At molecular level, we further defined that NKD1 is a major functional target of miR-744. Our findings indicate that miR-744 acts as one of oncogenic factor in the progression of CRPC by recruiting a mechanism of aberrant activation of Wnt/β-catenin signaling.

MicroRNA‑744 suppresses cell proliferation and invasion of papillary thyroid cancer by directly targeting NOB1

“…miR-744 upregulation inhibits cell proliferation and promotes cell cycle arrest in hepatocellular carcinoma (31). On the contrary, miR-744 serves oncogenic roles in prostate cancer (28), laryngeal squamous cell carcinoma (29), pancreatic cancer (27) and nasopharyngeal carcinoma (32). These findings indicate that the biological roles of miR-744 exhibit tissue specificity in tumorigenesis and tumour development.…”

“…miR-744 overexpression is significantly correlated with clinical stage, lymph node metastasis and recurrence (26). miR-744 has also been reported as an independent poor prognostic factor for patients with pancreatic cancer (26,27) and has exhibited high expression in prostate cancer (28), laryngeal squamous cell carcinoma (29) and nasopharyngeal carcinoma (30). These conflicting findings suggest that the expression profile of miR-744 exhibits tissue specificity in malignant tumors.…”

“…miRNAs serve crucial roles in the regulation of their target genes (33). Numerous human genes, including Notch1 (17), B-cell lymphoma 2 (18), secreted frizzled-related protein 1 precursor (27), glycogen synthase kinase 3β (27), transducing like enhancer of split 2 (27), naked cuticle homolog 1 (28), programmed cell death 4 (29), phosphatase and tensin homolog (29), c-myc (31) and Rho GTPase activating protein 5 (32), have been identified as direct miR-744 targets. In the present study, NOB1 was predicted as a direct target gene of miR-744 in PTC.…”

CRISPR/Cas9‐Mediated Knockout of MicroRNA‐744 Improves Antibody Titer of CHO Production Cell Lines

“…As miRNAs regulate cellular processes post‐transcriptionally via binding to target mRNAs, validated miR‐744 targets annotated in miRTarBase were investigated in relation to possible upregulation due to the absence of mature miR‐744 strands. Out of seven targets, CCNB1 and SFRP1 showed significant upregulation in two miR‐744 KO clones on transcription level. Nevertheless, relative quantification with qRT‐PCR only exhibits target mRNAs that are degraded by the miRNA‐guided RISC complex.…”

“…Interestingly, miR‐744 seems to mediate ambivalent effects depending on respective cancer tissue. Thus, proapoptotic impact was reported repeatedly, whereas others observed proproliferative properties of miR‐744 on cancer cells . Nevertheless, the clonal variability of CHO production cells frequently observed after generating clonal cell lines may also be considered and therefore a larger number of deletion and control clones should be analyzed to undermine observed functional improvements .…”