Mir-371, mir-150, mir-21 and mir-7d were found to be potential prognostic markers, while mir-134, mir-146a, mir-338 and mir-371 were associated with metastases.
Our findings suggest that miR-21 could be independent molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis.
MicroRNAs (miRs) play a key role in the pathogenesis of human malignancies and particularly in acute myeloid leukemias (AMLs) and are increasingly recognized as potential biomarkers and therapeutic targets. miR-21 is dysregulated in several types of cancers, including some hematologic malignancies, and plays a key role in carcinogenesis, disease recurrence and metastasis.
Meanwhile, mouse model of tumor peritoneal dissemination model was performed to investigate the role of exosomal miR-21-5p in peritoneal metastasis in vivo.
Mechanistically, miR-21-5p and miR-155-5p were transferred to colorectal cancer cells by MDE and bound to the BRG1 coding sequence, downregulating expression of BRG1, which has been identified as a key factor promoting the colorectal cancer metastasis, yet is downregulated in metastatic colorectal cancer cells.
Higher levels of serum miR-21 were also correlated with tumors of higher grades, more nodal involvement, distal metastasis and advanced clinical stages (p < 0.01).
Moreover, the expression levels of miR-182, miR-183, miR-141, and miR-21 were demonstrated to be associated with a gradual increase in fold change expression with depth of tumor invasion (all P < .05), lymph node invasion (all P < .001), and maximal increase with distant metastasis (all P < .001).
In the TCGA dataset, combined biomarkers associated with metastasis and overall survival (miR-21+142-5p+194: <i>P</i> < 0.0001; OR, 0.37; 95% CI, 0.58-0.23).<b>Conclusions:</b> The interconnected discovery-validation approach identified a three-miRNA signature as a potential predictor of disease outcome in RCC patients.<b>Impact:</b> With 10% survival at 5 years, metastatic disease presents poor prognosis for RCC patients.
Here we show that tumor-secreted miR-21 and miR-29a also can function by another mechanism, by binding as ligands to receptors of the Toll-like receptor (TLR) family, murine TLR7 and human TLR8, in immune cells, triggering a TLR-mediated prometastatic inflammatory response that ultimately may lead to tumor growth and metastasis.
The carcinogenic advantage generated by miR-21 in NSCLC resides in the target genes involved in multiple pathways such as cell growth and proliferation, angiogenesis, invasion and metastasis, but also chemo- and radioresistance.
More importantly, α-SMA and miR-21 are independent predictors of recurrence and metastasis, with their predictive value of recurrence better than histologic grading.
In addition, miR-21 downregulation induced by MMP-8 increases the levels of tumor suppressors such as programmed cell death 4, which may also contribute to the decrease in tumor formation and metastasis of breast cancer cells overexpressing this metalloproteinase.
Finally, we investigated the regulatory mechanism of XIST acting as a competitive endogenous RNA (ceRNA) of miR-21-5p in OS progression and metastasis. lncRNA XIST was significantly downregulated in osteosarcoma tissues and osteosarcoma cells, and associated with recurrence and short overall survival in OS patients.
The combined data for the prognostic meta-analysis (seven studies) suggested that miR-21 overexpression in HCC correlated with poor overall survival [HR = 1.19 (95%CI = 0.44-1.94)], and higher miR-21 expression was associated with tumor, node, metastases (TNM) stage [OR = 0.34 (95%CI = 0.13-0.91)].
The overexpression of miR-21, miR-10b, and miR-19a is associated with the acquisition of malignant characteristics (increased tumor cell proliferation, migration, invasion, dissemination, and metastasis); thus, we determined their utility as serum biomarkers for aggressive breast cancer (HER2-overexpressed or -amplified [HER2(+)] and inflammatory breast cancer [IBC]).
Using a mouse xenograft tumor model, we found that the overexpression of MEG3 suppressed tumor growth and metastasis while overexpression of miR‑21 had the opposite effects.
In particular, miR-21, an oncogenic miRNA is a major player involved in tumor initiation, progression, invasion and metastasis in several cancers, including triple negative breast cancer (TNBC).