Hsa-miR-21-3p associates with breast cancer patient survival and targets genes in tumor suppressive pathways

Abstract

Breast cancer is the cancer most often diagnosed in women. MicroRNAs (MIRs) are short RNA molecules that bind mRNA resulting in their downregulation. MIR21 has been shown to be an oncomiR in most cancer types, including breast cancer. Most of the effects of miR-21 have been attributed to hsa-miR-21-5p that is transcribed from the leading strand of MIR21, but hsa-miR-21-3p (miR-21-3p), transcribed from the lagging strand, is much less studied. The aim of the study is to analyze whether expression of miR-21-3p is prognostic for breast cancer. MiR-21-3p association with survival, clinical and pathological characteristics was analyzed in a large breast cancer cohort and validated in three separate cohorts, including TCGA and METABRIC. Analytical tools were also used to infer miR-21-3p function and to identify potential target genes and functional pathways. The results showed that in the exploration cohort, high miR-21-3p levels associated with shorter survival and lymph node positivity. In the three validation cohorts, high miR-21-3p levels associated with pathological characteristics that predict worse prognosis. Specifically, in the largest validation cohort, METABRIC (n = 1174), high miR-21-3p levels associated with large tumors, a high grade, lymph node and HER2 positivity, and shorter breast-cancer-specific survival (HR = 1.38, CI 1.13–1.68). This association remained significant after adjusting for confounding factors. The genes with expression levels that correlated with miR-21-3p were enriched in particular pathways, including the epithelial-to-mesenchymal transition and proliferation. Among the most significantly downregulated targets were MAT2A and the tumor suppressive genes STARD13 and ZNF132. The results from this study emphasize that both 3p- and 5p-arms from a MIR warrant independent study. The data show that miR-21-3p overexpression in breast tumors is a marker of worse breast cancer progression and it affects genes in pathways that drive breast cancer by down-regulating tumor suppressor genes. The results suggest miR-21-3p as a potential biomarker.

miRNAs in Cancer (Review of Literature)

“…Examination of miRNAs for specific fractions can significantly increase both the sensitivity and specificity of selected circulating miRNAs as noninvasive biomarkers [ 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ].…”

A novel N7-methylguanosine(m7G) methylation-associated miRNA signature for prognostic value in patient with carcinoma of colon

“…The 14 miRNAs were correlated with the prognosis of patients with carcinoma of colon. However, other researchers have reported that upregulation of hsa-miR-194-3p was associated with the early T-stages [41].Studies have shown that high levels of mir-21-3p are associated with short survival time, poor prognosis, pathological features and positive lymph nodes [42]. Its overexpression in breast tumors is a sign of disease deterioration.…”

A Novel N7-Methylguanosine (M7g) Methylation-Associated Mirna Signature for Prognostic Value in Patient with Carcinoma of Colon

“…However, other researchers have reported that upregulation of hsa-miR-194-3p was associated with the early T-stages [41]. Genes Hen G, etl found that hsa-miR-200c-5p was key regulator in HCV-HCC development by analyzing transcriptome-sequencing data [42,43]. Up-regulation of hsa-miR-221-3p affects proliferation and apoptosis of cells via Bcl-xL/Bax pathway.…”