Interestingly, we identified one regulatory feedback loop between STAT1 and miR-155-5p that is consistently activated in all seven cancer types with its function to regulate tumor-related biological processes.
Mir -10b, mir -21, mir-155 and mir373 and the metastatic genes MMP2, MMP9 and VEGF were significantly associated with an increase in tumor size (P<0.05).
Four oncogenic microRNAs (miR-155, miR-19a, miR-181b, and miR-24) and one tumor suppressor microRNA (let-7a) were shown to differentiate between high- and low-risk early breast cancer (EBC) and reflect the surgical tumor removal and adjuvant therapy.
By gain- and loss-of-function analysis, we determined that CCAT1 repressed monocytic differentiation and promoted cell growth of HL-60 by sequestering tumor suppressive miR-155.
Clinical association analysis revealed that high expression of miR-155 was correlated with malignant clinicopathological characteristics including large tumor size, high Edmondson-Steiner grading and TNM tumor stage.
Human cancers commonly exhibit an altered expression profile of miRNAs with oncogenic (miR-21, miR-106a and miR-155) or tumor-suppressive (let-7, miR-15a/16, miR-34a and miR-143/145) activity.
They found that decreased miR-31 and miR-214 and increased miR-155 expression can reprogram normal fibroblasts into tumor-promoting cancer-associated fibroblasts.
By simultaneously targeting tumor suppressor genes and inducing a mutator phenotype, miR-155 may allow the selection of gene alterations required for tumor development and progression.
Our data showed that a common pattern of microRNA expression distinguishes any tumor type from normal pancreas, suggesting that this set of microRNAs might be involved in pancreatic tumorigenesis; the expression of miR-103 and miR-107, associated with lack of expression of miR-155, discriminates tumors from normal; a set of 10 microRNAs distinguishes endocrine from acinar tumors and is possibly associated with either normal endocrine differentiation or endocrine tumorigenesis; miR-204 is primarily expressed in insulinomas and correlates with immunohistochemical expression of insulin; and the overexpression of miR-21 is strongly associated with both a high Ki67 proliferation index and presence of liver metastasis.
Targeting CD47/TNFAIP8 by miR-155 overcomes drug resistance and inhibits tumor growth through induction of phagocytosis and apoptosis in multiple myeloma.
These cells resembled tumors with a low methylation of the miR-155 promoter and thus mir-155 or NFκB inhibition may provide treatment options with a special focus on patients with IDH wild type tumors.
Cancer-associated microRNAs can act as both tumour suppressor molecules (e.g., miR-15a and miR-16-1) and have oncogenic properties (e.g., miR-155 and miR-17-92 cluster).
In a recent report, BRCA1-mediated epigenetic repression at the promoter region of miRNA-155 was identified as a novel mechanism by which BRCA1 carries out its tumor suppressor functions.
Using a powerful, inducible transgenic mouse model that overexpresses miR-155 and develops miR-155-addicted hematological malignancy, we describe here a multi-step process of oncogenesis by miR-155, which involves cooperation between miR-155, its direct targets, and other oncogenes. miR-155 is known to target DNA-repair proteins, leading to a mutator phenotype, and we find that over 93% of tumors in our miR-155 overexpressing mice contain activating mutations in a single oncogene, c-Kit.
To the best of our knowledge, the present study is the first to examine the expression patterns of miR-21 and miR-155 as an adjunctive diagnostic tool or clinically relevant biomarkers for pulmonary NE tumors.
The finding that the expression of the putative tumor suppressor SEL1L is repressed by upregulation of hsa-mir-155 helps to elucidate the mechanism for SEL1L downregulation in some human PDA cases.
In addition, miR-21 and miR-155 share nearly 30% of their predicted target genes, including SOCS1, SOCS6, and PTEN, three tumor suppressor genes often silenced in NSCLC.