Identifying a miRNA signature for predicting the stage of breast cancer

Sathipati, Srinivasulu Yerukala; Ho, Shinn-Ying

doi:10.1038/s41598-018-34604-3

Cited by 92 publications

(55 citation statements)

References 84 publications

(85 reference statements)

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“…Another relevant observation ensuing from NGS results is that miRNA levels are dynamic and are changing with time, and the same miRNAs that are deregulated in earlier stages of the tumor are not the same that are deregulated in more advanced stages, except for a small number of miRNAs that are deregulated throughout the metastatic development. This is supported by a recent study, showing that miRNA expression profiles can efficiently distinguish and categorize BC patients into early and advanced stages (Yerukala Sathipati and Ho, ).…”

Section: Discussionsupporting

confidence: 58%

Downregulation of circulating miR 802‐5p and miR 194‐5p and upregulation of brain MEF2C along breast cancer brain metastasization

et al. 2020

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Breast cancer brain metastases (BCBMs) have been underinvestigated despite their high incidence and poor outcome. MicroRNAs (miRNAs), and particularly circulating miRNAs, regulate multiple cellular functions, and their deregulation has been reported in different types of cancer and metastasis. However, their signature in plasma along brain metastasis development and their relevant targets remain undetermined. Here, we used a mouse model of BCBM and next‐generation sequencing (NGS) to establish the alterations in circulating miRNAs during brain metastasis formation and development. We further performed bioinformatics analysis to identify their targets with relevance in the metastatic process. We additionally analyzed human resected brain metastasis samples of breast cancer patients for target expression validation. Breast cancer cells were injected in the carotid artery of mice to preferentially induce metastasis in the brain, and samples were collected at different timepoints (5 h, 3, 7, and 10 days) to follow metastasis development in the brain and in peripheral organs. Metastases were detected from 7 days onwards, mainly in the brain. NGS revealed a deregulation of circulating miRNA profile during BCBM progression, rising from 18% at 3 days to 30% at 10 days following malignant cells’ injection. Work was focused on those altered prior to metastasis detection, among which were miR‐802‐5p and miR‐194‐5p, whose downregulation was validated by qPCR. Using targetscan and diana tools, the transcription factor myocyte enhancer factor 2C (MEF2C) was identified as a target for both miRNAs, and its expression was increasingly observed in malignant cells along brain metastasis development. Its upregulation was also observed in peritumoral astrocytes pointing to a role of MEF2C in the crosstalk between tumor cells and astrocytes. MEF2C expression was also observed in human BCBM, validating the observation in mouse. Collectively, downregulation of circulating miR‐802‐5p and miR‐194‐5p appears as a precocious event in BCBM and MEF2C emerges as a new player in brain metastasis development.

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Section: Discussionsupporting

confidence: 58%

Downregulation of circulating miR 802‐5p and miR 194‐5p and upregulation of brain MEF2C along breast cancer brain metastasization

et al. 2020

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“…Two of the metastatic group-related miRNAs, hsa-miR-1247 and hsa-miR-592, have been previously described as upregulated in high-grade uveal melanoma, by Falzone et al [18]. These results are contrary to several other studies showing that they usually act as tumor suppressors in pancreatic, colorectal, prostate, breast, and other cancers [21][22][23][24][25][26]. Similar to our studies, the overexpression of hsa-miR-592 was also described in progression of renal cell carcinoma, colorectal carcinoma with unaffected mismatch repair mechanisms, and gastric cancer [27][28][29].…”

Section: Discussionmentioning

confidence: 91%

The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression

Wróblewska

Lach

Ustaszewski

et al. 2020

Genes

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Uveal melanoma (UM) is the most common primary tumor of the eye diagnosed in adults, associated with a high risk of metastasis and thereby, poor prognosis. Among known risk factors for the development of metastatic disease is the loss of BAP1 expression and chromosome 3 monosomy in the primary tumor. However, the expression levels of specific micro RNAs (miRNA) in tumor tissue may also serve as a valuable marker for determining the risk of metastatic disease in patients with primary uveal melanoma. In our study, we analyzed the miRNA expression data of cases selected from The Cancer Genome Atlas study on uveal melanoma, and determined a panel of 15 miRNAs differentially expressed between patients with primary and metastatic disease. Next, 6 miRNAs were validated on a group of 46 tumor samples from primary and metastatic patients. We have shown, that expression of hsa-miR-592, hsa-miR-346, and hsa-miR-1247 was significantly increased, while hsa-miR-506 and hsa-miR-513c were decreased in the tumors of patients with metastatic disease. Hsa-miR-196b expression did not differ between the two subgroups, however, we showed significant correlation with BAP1 expression. Moreover, hsa-miR-592 also showed correlation with monosomy 3 tumors. Gene ontology analysis revealed involvement of those miRNAs with cellular processes mediating the metastatic process. Our results showed that miRNAs play an important role in the deregulation of several oncogenic pathways in UM and can, thereby, promote metastatic spread to distant organs. Moreover, differentially expressed miRNAs may be used as an interesting biomarker for the assessment of metastatic risk in uveal melanoma patients.

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“…Despite surgical resection combined with radiotherapy or chemotherapy being effective in improving the prognosis of patients with breast carcinoma, those patients who have distant metastasis and recurrence after the surgical resection have high mortality rates . Accordingly, the identification of molecules involved in breast cancer tumorigenesis and metastasis is helpful for developing new potential targets to treat breast cancer .…”

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confidence: 99%

miRNA‐215‐5p suppresses the aggressiveness of breast cancer cells by targeting Sox9

Gao

Zhu

2019

FEBS Open Bio

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Several studies have shown that miR‐215‐5p acts as a tumor suppressor in certain cancers, but its role in the progression and metastasis of breast carcinoma remains incompletely understood. Herein, we prove that miR‐215‐5p is substantially down‐expressed in breast carcinoma as compared with nontumor tissue. Up‐regulation of miR‐215‐5p inhibits the aggressive abilities of breast carcinoma cells in vitro. We performed luciferase reporter tests to show that SRY‐Box 9 (Sox9) is the target of miR‐215‐5p; as predicted, Sox9 depletion replicates the suppressive effects of miR‐215‐5p on breast carcinoma cells, and overexpression of Sox9 rescues the effects of miR‐215‐5p on breast cancer cell progression. In addition, a xenograft model assay was used to reveal that miR‐215‐5p inhibits breast cancer cell growth and metastatic potential in vivo. Overall, these results imply that miRNA‐215‐5p suppresses the aggressiveness of breast cancer cells through targeting Sox9.

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Identifying a miRNA signature for predicting the stage of breast cancer

Cited by 92 publications

References 84 publications

Downregulation of circulating miR 802‐5p and miR 194‐5p and upregulation of brain MEF2C along breast cancer brain metastasization

Downregulation of circulating miR 802‐5p and miR 194‐5p and upregulation of brain MEF2C along breast cancer brain metastasization

The Potential Role of Selected miRNA in Uveal Melanoma Primary Tumors as Early Biomarkers of Disease Progression

miRNA‐215‐5p suppresses the aggressiveness of breast cancer cells by targeting Sox9

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