Prognostic value of Dicer expression in human breast cancers and association with the mesenchymal phenotype

Abstract

BACKGROUND: Dicer, a ribonuclease, is the key enzyme required for the biogenesis of microRNAs and small interfering RNAs and is essential for both mammalian development and cell differentiation. Recent evidence indicates that Dicer may also be involved in tumourigenesis. However, no studies have examined the clinical significance of Dicer at both the RNA and the protein levels in breast cancer. METHODS: In this study, the biological and prognostic value of Dicer expression was assessed in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterised sets of breast carcinoma samples obtained from patients with long-term follow-up using tissue microarrays and quantitative reverse transcription -PCR. RESULTS: We have found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumours (ER P ¼ 0.008; PR P ¼ 0.019; cancer subtype P ¼ 0.023, luminal A P ¼ 0.0174). Dicer mRNA expression appeared to have an independent prognostic impact in metastatic disease (hazard ratio ¼ 3.36, P ¼ 0.0032). In the breast cancer cell lines, lower Dicer expression was found in cells harbouring a mesenchymal phenotype and in metastatic bone derivatives of a breast cancer cell line. These findings suggest that the downregulation of Dicer expression may be related to the metastatic spread of tumours. CONCLUSION: Assessment of Dicer expression may facilitate prediction of distant metastases for patients suffering from breast cancer.

MicroRNA Biogenesis and Hedgehog-Patched Signaling Cooperate to Regulate an Important Developmental Transition in Granule Cell Development

“…Dicer1 functions as a haploinsufficient tumor suppressor gene in Ptch1-induced medulloblastoma DICER1 has previously been reported to function as a haploinsufficient tumor suppressor gene in human tumors (Karube et al 2005;Chiosea et al 2007;Merritt et al 2008;Grelier et al 2009;Faggad et al 2010;Lin et al 2010;Khoshnaw et al 2012;Jafarnejad et al 2013) and genetically engineered mouse models (Kumar et al 2009;Lambertz et al 2010), with only a handful of exceptions (Arrate et al 2010;Sabbaghian et al 2012;Zhang et al 2013). The precise role of DICER1 in medulloblastoma is less clear.…”

MicroRNAs and Breast Cancer

“…A recent study examined the biological and prognostic value of Dicer expression at both the RNA and protein level in breast cancer cell lines, breast cancer progression cellular models, and in two well-characterized sets of breast carcinoma samples obtained from patients with long-term followup using tissue microarrays and quantitative reverse transcription-PCR [27]. In summary, the study found that Dicer protein expression is significantly associated with hormone receptor status and cancer subtype in breast tumors (ER p=0.008; PR p=0.019; cancer subtype p=0.023, luminal A p=0.0174).…”

MicroRNA-mediated breast cancer metastasis: from primary site to distant organs

“…Frequent deletion of Dicer1 was observed in the human cancer genome, and enforced Dicer1 deletion caused the inhibition of tumorigenesis . A low level of Dicer was also observed in breast cancer cell lines with a mesenchymal phenotype or with distinct metastatic bone derivatives (Grelier et al, 2009). These observations indicate a dual role of Dicer in cancer: it is essential for proliferation and cell survival but is a barrier against metastatic spread to distinct organs.…”