Dysregulated expression of Dicer in invasive ductal breast carcinoma

Abstract

Several lines of evidence suggest that the global down-regulation of the microRNAome (miRNAome) involved in pathogenesis of various malignancies. Impaired microRNAs processing pathway is one possible mechanism for global down-regulation of the miRNAome. Dicer is a key enzyme in miRNA processing pathway, and dysregulation of its expression has been suggested as a possible cause of miRNAome alterations observed in various cancers. However, Dicer mRNA expression in invasive ductal breast carcinoma (IDC) has not been investigated in depth. Therefore, this study aimed to evaluate the mRNA expression of Dicer in IDC and also to assess the correlation of its expression with clinicopathological parameters including age, histological grade, tumor size and lymph node metastasis. We investigated the expression of the Dicer in seventy fresh invasive ductal breast carcinomas and matched adjacent non-neoplastic tissue by quantitative real-time PCR using validated reference genes. In addition, the possible impact of clinicopathological characteristics on Dicer expression levels was analyzed. Our results showed that Dicer mRNA expression is down-regulated in slightly more than half (51.43 %) of the tumor specimens when compared to adjacent non-neoplastic tissue. Comparison of the Dicer expression level between tumor and matched adjacent non-neoplastic tissue showed that there is no statistical significant differences between them (P = 0.425). We also found that Dicer mRNA expression in IDC samples was not correlated with clinicopathological features. In conclusion, our findings provide additional evidence to support the hypothesis that Dicer expression down-regulated in breast cancer. This study suggested that the decreased expression of Dicer may be potential underlying mechanism in pathogenesis of IDC.

Tamoxifen differentially regulates miR-29b-1 and miR-29a expression depending on endocrine-sensitivity in breast cancer cells

“…Because of its role in microRNA processing from pre-miRs to mature microRNAs, DICER1 regulates cellular processes including cell differentiation, programmed cell death, senescence, DNA repair, and chromatin remodeling [52-56]. DICER1 expression was reported to be downregulated in breast cancer cells exhibiting mesenchymal phenotypes and in primary breast tumors of patients with lower disease free survival [57].…”

“…DICER1 mRNA expression was decreased in breast cancer tissues [59] and in invasive ductal breast carcinomas [52]. In ERα negative breast cancer cells, DICER1 is repressed by tumor promoting microRNAs including miR-103/107 [60], miR-222/221 [40], and miR-18a [61].…”

Racial Differences in Expression Levels of miRNA Machinery-Related Genes, Dicer, Drosha, DGCR8, and AGO2, in Asian Korean Papillary Thyroid Carcinoma and Comparative Validation Using the Cancer Genome Atlas

“…Among these diseases, aberrant expression levels of miRNA machinery components are implicated in carcinogenesis. For example, Dicer, the key enzyme in the miRNA machinery, is dysregulated in acute myeloid leukemia [ 12 ], hepatocellular carcinoma [ 13 ], invasive ductal breast carcinoma [ 14 ], ovarian serous carcinoma [ 15 ], pleomorphic adenomas of the salivary gland [ 16 ], and prostate adenocarcinoma [ 17 ]. Additionally, Drosha, a part of the microprocessor complex, is dysregulated in cervical squamous cell carcinoma [ 18 ], colorectal carcinoma [ 19 ], endometrial cancers [ 20 ], and metastatic serous ovarian carcinoma [ 21 ].…”

MicroRNAs and Growth Factors: An Alliance Propelling Tumor Progression

“…In line with global alterations, it has been shown that malignant processes involve dysregulation or dysfunction of the miRNA biogenesis machinery due to mutations or epigenetic events (reviewed by [ 27 ] and by [ 28 ]). For example, expression of Drosha and/or Dicer is decreased in some tumor types, including neuroblastoma, liposarcoma, lung, breast, and ovarian cancers [ 29 , 30 , 31 ]. Growth factor signaling pathways, such as the epidermal growth factor receptor (EGFR) and the transforming growth factor beta (TGF-β) pathways, might affect general processing of miRNAs.…”