MicroRNA Profiling of Salivary Duct Carcinoma Versus Her2/Neu Overexpressing Breast Carcinoma Identify miR-10a as a Putative Breast Related Oncogene

Abstract

<p class="first" id="Par1">Salivary duct carcinomas (SDC) and Her2/Neu3-overexpressing invasive breast carcinomas (HNPIBC/IBC) are histologically indistinguishable. We investigated whether common histopathologic and immunophenotypic features of SDC and IBC are mirrored by a similar microRNA (miRNA) profile. MiRNA profiling of 5 SDCs, 6 IBCs Her2/Neu3+, and 5 high-grade ductal breast carcinoma in situ (DCIS) was performed by NanoString platform. Selected miRNAs and <i>HOXA1</i> gene were validated by RT-PCR. We observed similar miRNA expression profiles between IBC and SDC with the exception of 2 miRNAs, <i>miR-10a</i> and <i>miR-142-3p</i>, which were higher in IBC tumors. DCIS tumors displayed increased expression of <i>miR-10a, miR-99a, miR-331-3p</i> and <i>miR-335</i>, and decreased expression of <i>miR-15a, miR-16</i> and <i>miR-19b</i> compared to SDC. The normal salivary gland and breast tissues also showed similar expression profiles. Interestingly, <i>miR-10a</i> was selectively increased in both IBC and normal breast tissue compared to SDC and normal salivary gland tissue. Moreover, our NanoString and RT-PCR data confirmed that <i>miR-10a</i> was upregulated in IBC and DCIS compared to SDC. Finally, we show downregulation of <i>HOXA1</i>, a <i>miR-10</i> target, in IBC tumors compared to normal breast tissue. Taken together, our data demonstrates that, based on miRNA profiling, SDC is closely related to HNPIBC. Our results also suggest that <i>miR-10a</i> is differentially expressed in IBC compared to SDC and may have potential utility as a diagnostic biomarker in synchronous or metachronous malignant epithelial malignancies involving both organs. In addition, <i>miR-10a</i> could be playing an important role as a mammary-specific oncogene, involved in breast cancer initiation (DCIS) and progression (IBC), through mechanisms that include modulation of <i>HOXA1</i> gene expression. </p><div class="section"> <a class="named-anchor" id="d5612207e266"> <!-- named anchor --> </a> <h5 class="section-title" id="d5612207e267">Electronic supplementary material</h5> <p id="d5612207e269">The online version of this article (10.1007/s12105-018-0971-x) contains supplementary material, which is available to authorized users. </p> </div>