MiR-154 inhibits cells proliferation and metastasis in melanoma by targeting AURKA and serves as a novel prognostic indicator.

Abstract

OBJECTIVE:

Increasing evidence suggested that dysregulated miR-154 in several tumor tissues is involved in the clinical progress of cancers patients. The objective of this study was to explore the expression pattern of miR-154 and its potential effects in human melanoma.

PATIENTS AND METHODS:

Microarray data from GEO datasets were analyzed to identify differentially expressed miRNAs. Real Time-Polymerase Chain Reaction (RT-PCR) was performed to determine the expressions of miR-154 in melanoma cell lines and tumor tissues. The associations between miR-154 levels and clinical progress were studied using a series of statistical methods. Cell viability, invasion, migration, and apoptosis were detected by Cell Counting Kit-8 (CCK-8) assays, transwell assay, wound healing assays, and flow cytometry, respectively. TargetScan system was used to identify the target genes of miR-154 and Luciferase activity analysis was carried out to demonstrate the possible target.

RESULTS:

The expression levels of miR-154 were distinctly lower in tumor samples and melanoma cell lines than in normal controls (p < 0.01). The up-regulation of miR-154 in melanoma tissues was associated with advanced tumor stage (p = 0.028), ulceration (p = 0.046), and shorter overall survival (p = 0.0035). Moreover, the multivariate analysis suggested a decreased expression of miR-154 is an independent predictor of overall survival rates in melanoma patients. Functional observation showed that up-regulation of miR-154 suppressed the capability of proliferation, invasion, and migration, promoting apoptosis in melanoma cell lines. Bioinformatics analysis predicted AURKA (aurora kinase A) as a target of miR-154, which was confirmed using the luciferase activity assays. Besides, miR-154 overexpression rescued the suppressive effect of AURKA-mediated melanoma on cell proliferation, colony formation, and metastasis.

CONCLUSIONS:

These results revealed that miR-154 has clinical implications for targeted therapy of melanoma patients and indicated that miR-154 could represent a novel biomarker in predicting the clinical outcome for melanoma.

• Authors: J Wang, Y Fang, Y-F Liu, X Wang, X-L Wang, R-Y Wang, Z-D Meng
• Journal: European review for medical and pharmacological sciences (Eur Rev Med Pharmacol Sci) Vol. 23 Issue 10 Pg. 4275-4284 (May 2019) ISSN: 2284-0729 [Electronic] Italy
• PMID: 31173299 (Publication Type: Journal Article)

Chemical References

• Biomarkers, Tumor
• MIRN154 microRNA, human
• MicroRNAs
• AURKA protein, human
• Aurora Kinase A

Topics

• Adult
• Aurora Kinase A (biosynthesis, genetics)
• Biomarkers, Tumor (blood, genetics)
• Cell Count
• Cell Line, Tumor
• Cell Proliferation
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Humans
• Male
• Melanoma (genetics, pathology)
• MicroRNAs (genetics)
• Neoplasm Invasiveness (genetics)
• Neoplasm Metastasis
• Prognosis
• Survival Analysis
• Tumor Stem Cell Assay
• Up-Regulation