High expression of miR-21 in tumor stroma correlates with increased cancer cell proliferation in human breast cancer

Abstract

Low-risk and high-risk breast cancer patients are stratified primarily according to their lymph node (LN) status and grading. However, some low-risk patients relapse, and some high-risk patients have a favorable clinical outcome, implying a need for better prognostic and predictive tests. Micro RNAs are often aberrantly expressed in cancer and microRNA-21 is upregulated in a variety of cancers, including breast cancer. High miR-21 levels have been associated with poor prognosis. To determine the cellular localization of miR-21 and to compare its expression levels with histopathological features, we performed in situ hybridization and semi-quantitative assessment of the miR-21 signal on 12 LN negative grade I (assumed low risk), and 12 LN positive grade II (high risk) breast cancers. miR-21 was predominantly seen in cancer associated fibroblast-like cells, with no difference in expression levels between grade I and grade II carcinomas. Immunohistochemical scoring of the prognostic proliferation marker Ki-67 and tumor suppressor p53 showed that the miR-21 expression levels significantly correlated with the Ki-67 score (p = 0.043), whereas no correlation between p53 and miR-21 was found. Our results indicate that miR-21 may contribute to improve clinical stratification according to growth rate and facilitate tailored treatment of breast cancer patients.

miR-21 promotes migration and invasion by the miR-21-PDCD4-AP-1 feedback loop in human hepatocellular carcinoma

“…As an oncomir, miR-21 is upregulated in a variety of human malignancies, such as cholangiocarcinoma, breast cancer, lung cancer, colorectal cancer, and prostatic carcinoma (8)(9)(10)(11)(12). Consistent with these studies, we demonstrated that miR-21 expression was significantly higher in HCC tissues and cell lines than that in matched non-tumor tissues and normal human hepatic cells, suggesting that high miR-21 expression was tightly associated with tumor development.…”

“…Consistent with these studies, we demonstrated that miR-21 expression was significantly higher in HCC tissues and cell lines than that in matched non-tumor tissues and normal human hepatic cells, suggesting that high miR-21 expression was tightly associated with tumor development. Inhibition of miR-21 expression could restrain tumor growth in breast cancer cells (9), while overexpression of miR-21 could increase cell invasion in colon carcinoma (12). In this study, we observed that miR-21 expression was dramatically increased in invasive/metastatic HCC tumor tissues and tumor tissues from stage II-IV patients, as compared with that in non-invasive/non-metastatic HCC tumor tissues and tumor tissues from stage I-II patients.…”

“…Aberrant miRNA expression has been linked to human diseases, including cancer. As an oncogene, microRNA-21 (miR-21) was found to be overexpressed in a variety of malignancies, including cholangiocarcinoma (8), breast cancer (9), lung cancer (10), prostatic carcinoma (11) and colon carcinoma (12). miR-21 has also been implicated in multiple malignancyrelated processes, including cell proliferation, apoptosis, invasion and metastasis, by downregulating the expression of specific target genes, such as phosphatase and tensin homologue (PTEN), tropomyosin 1 (TPM1), programmed cell death 4 (PDCD4) and B-cell lymphoma 2 (Bcl-2) (13)(14)(15)(16).…”

Expression Analysis of MiR-21, MiR-205, and MiR-342 in Breast Cancer in Iran

“…P53 protein was stabilized by HNRPK that interferes with MDM2 (Papagiannakopoulos et al, 2008). Previous studies showed no significant correlation between P53 and miR-21 (Rask et al, 2011). It is known that certain missense mutations of P53 lead to a longer half life for the protein, which its accumulation in the cells can be detected with specific antibody.…”

Dicer1 imparts essential survival cues in Notch-driven T-ALL via miR-21–mediated tumor suppressor Pdcd4 repression

“…To date there are no reports on the role of miR-21 in thymocyte development or T-ALL; miR-21 has been described as an oncogene in several solid tumors. [51][52][53] Importantly, miR-21 function has been linked to cancer-related processes in hepatocellular, glioblastoma, and breast cancer. 33,[54][55][56] Furthermore, microarray analysis of miR-21 target gene expression in BM aspirates of T-ALL patients and normal controls revealed that many miR-21 targets were repressed in T-ALL patient samples, indicative of a clinical relevance of miR-21 target gene repression in T-ALL.…”