Downregulation of Hsa-miR-3616-3p in Triple-Negative Breast Cancer is Associated with Cell Migration and Invasion

Abstract

Background: Micro RNA (miRNA), a class of endogenous small RNAs with a length of about 20-24 nucleotides, have been played a variety of important regulatory roles in cells and have attracted the attention of researchers because involvement of initiation and progression of diverse kinds of human diseases, especially cancer. However, the regulatory role of miRNA in triple negative breast cancer (TNBC), its clinical significance and potential mechanism are still largely unknown.Methods: In this study, the differentially expressed miRNAs were analyzed using GEO2R from GSE57897 and GSE97811 of the Gene Expression Omnibus (GEO). Then, we performed the overall survival (OS) analysis of four candidate miRNAs. And the expressions of four candidate miRNAs in TNBC and non-TNBC tissues were tested by Quantitative real-time PCR. We determined the level and prognostic values of hsa-miR-3616-3p in TNBC patients. Then, TNBC cells migration and invasion were studied in vitro with hsa-miR-3616-3p by using wounding heal assays and transwell assays. Next, target genes and transcription factors of hsa-miR-3616-3p enrichment analysis, were performed by the Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway.Results: Based on GSE57897 and GSE97811, we found 962 differentially expressed miRNAs including 943 up-regulated miRNAs and 19 down-regulated miRNAs. We selected top2 up-regulated miRNAs as hsa-miR-4428 and hsa-miR-575, and top2 down-regulated miRNAs as hsa-miR-3616-3p and hsa-miR-3909, and then we found that low expression of 4 candidated miRNAs had a worse prognosis in TNBC subtype. Next, we verified that the expression of hsa-miR-3616-3p was the most downregulated in TNBC tissues compared with matched surrounding tissues by qRT-PCR. Moerover, our results showed that overexpression of hsa-miR-3616-3p inhibited TNBC cells migration, and invasion in vitro.Conclusions: Our study might reveal important roles of hsa-miR-3616-3p plays in TNBC migration and invasion.

Construction of a miRNA-Based Nomogram Model to Predict the Prognosis of Endometrial Cancer

“…Similar to our study, Lu et al also pointed out that has-mir-3614 is low-expressed in endometrial cancerous tissue [53]. A previous study had showed that the low-expression of has-mir-3616 contributes to triple negative breast cancer migration and invasion [54], and at the same time, low-expression of hsamir-3616 was also found to significantly reduce the survival rate of EC patients in this study (p < 0.001), which may be related to the expression of target mRNA. Translational inhibition or destabilization causes immunosuppression that forms the tumor microenvironment, and this can further be explored as potential targets of EC-related miRNAs.…”