MiRNA expression in breast cancer varies with lymph node metastasis and other clinicopathologic features

Abstract

Breast carcinoma is the most common malignant tumor in females, and lymph node (LN) status is one of the most important prognostic factors in patients with breast cancer. MiRNAs have been shown to have important role in oncogenesis, invasion, and metastasis via epigenetic posttranscriptional gene regulation. However, lymphatic metastasis-related miRNAs of breast cancer has not been well documented. The aim of this study was to identify and evaluate miRNAs related to breast cancer LN metastasis and to explore the clinical significance of the differentially expressed miRNAs in patients with breast cancer. The expression of miRNAs in patients with primary breast cancer with LN metastasis and that without LN metastases was compared by miRNA microarray. We further validated the miRNAs (miR-185-5p, miR-339-5p, miR-542-5p, and miR-3923) between LN (n 5 31) and nonlymph node (NLN; n 5 42) group using real-time reverse transcriptase polymerase chain reaction. Furthermore, the relationship between miRNA expression and clinical pathological features was analyzed. The miRNA microarray initially identified that eight miRNAs (miR-206, miR-3923, miR-181a, miR-92a, miR-421, miR-339-5p, miR-3196, and miR-29b) were downregulated in LN metastasis group, whereas five miRNAs (miR-542-5p, miR-200a, miR-564, miR-451, miR-30c, miR-200b, miR-191-3p, miR-142-5p, and miR-185-5p) were upregulated in LN group when compared with those in NLN group. In the validation cohort, the expression levels of miR-185-5p and miR-542-5p were significantly expressed higher in LN group (P 5 0.002 and P 5 0.001, respectively), and the expression levels of miR-339-5p and miR-3923 were significantly expressed lower in LN group (P 5 0.001 and P 5 0.001, respectively). Our results indicate the potential role of miR-185-5p, miR-542-5p, miR-339-5p, and miR-3923 in predicting metastasis to the LN and prognosis in breast cancers.

Transcriptome sequencing uncovers a three–long noncoding RNA signature in predicting breast cancer survival

“…Most of the 15 miRNAs were reported to link with breast cancer. For instance, let-7 , miR-379 , miR-381 , and miR-421 were found to be down-regulated in breast cancer25262728; miR-17 , miR-18a , and miR-9 turned out to be metastasis-associated293031; and miR-190 was detected to be related to estrogen receptor32. In addition, the functional enrichment of target mRNA showed that target mRNAs of these miRNAs were significantly ( P  < 0.01) enriched in the pathway related to cancer, such as pathways in cancer, ubiquitin-mediated proteolysis, and MAPK signaling pathway (Table S7).…”

miR-564 is downregulated in gastric carcinoma and targets E2F3

“…RT-qPCR analysis of 8 GC tissue and adjacent normal tissue samples validated that miR-564 was downregulated in GC, which was consistent with the results of miRNA microarray analysis. miR-564 has been reported to be aberrantly expressed in breast cancer (31) and chronic myeloid leukemia (32), indicating that is serves a role in cancer development. However, the molecular mechanism underlying the downregulation of miR-564 in GC remains unknown.…”

The Dual Regulatory Role of MiR-181a in Breast Cancer

“…Moreover, lymph node involvement in breast cancer is indicative of high-grade, late-stage advanced disease. In breast cancers where a lymph node could be identified using realtime RT-PCR (n=31), miR-181a was one of the eight miRNAs that was downregulated when compared to the non-lymph node (n = 42) group [32]. …”