MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer

Milevskiy, Michael J. G.; Sandhu, Gurveen K; Wronski, Ania; Korbie, Darren; Brewster, Brooke L.; Shewan, Annette M.; Edwards, Stacey L.; French, Juliet D.; Brown, Melissa A.

doi:10.18632/oncotarget.26094

Cited by 17 publications

(18 citation statements)

References 53 publications

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“…Notably, through dampening cell survival, the overexpression of miR-24-2 reduces the growth of BC [48]. Also, miR-29b1 and miR-639 have been demonstrated to be informative 14 Disease Markers biomarkers associated with the survival and recurrence of BC patients in related researches [49,50]. The other three genes, miR-5001, miR-514a-1, and miR-6892, have not been individually studied.…”

Section: Discussionmentioning

confidence: 99%

Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer

Tang

Zeng³

et al. 2019

Disease Markers

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To identify the novel, noninvasive biomarkers to assess the outcome and prognosis of breast cancer (BC), patients with high sensitivity and specificity are greatly desired. Herein, the miRNA expression profile and matched clinical features of BC patients were extracted from The Cancer Genome Atlas (TCGA) database. The preliminary candidates were screened out by the univariate Cox regression test. Then, with the help of LASSO Cox regression analysis, the hsa-let-7b, hsa-mir-101-2, hsa-mir-135a-2, hsa-mir-22, hsa-mir-30a, hsa-mir-31, hsa-mir-3130-1, hsa-mir-320b-1, hsa-mir-3678, hsa-mir-4662a, hsa-mir-4772, hsa-mir-493, hsa-mir-556, hsa-mir-652, hsa-mir-6733, hsa-mir-874, and hsa-mir-9-3 were selected to construct the overall survival (OS) predicting signature, while the hsa-mir-130a, hsa-mir-204, hsa-mir-217, hsa-mir-223, hsa-mir-24-2, hsa-mir-29b-1, hsa-mir-363, hsa-mir-5001, hsa-mir-514a-1, hsa-mir-624, hsa-mir-639, hsa-mir-659, and hsa-mir-6892 were adopted to establish the recurrence-free survival (RFS) predicting signature. Referring to the median risk scores generated by the OS and RFS formulas, respectively, subgroup patients with high risk were strongly related to a poor OS and RFS revealed by Kaplan-Meier (K-M) plots. Meanwhile, receiver operating curve (ROC) analysis validated the accuracy and stability of these two signatures. When stratified by clinical features, such as tumor stage, age, and molecular subtypes, we found that the miRNA-based OS and RFS classifiers were still significant in predicting OS/RFS and showed the best predictive values than any other features. Besides, functional prediction analyses showed that these targeted genes of the enrolled miRNAs were enriched in cancer-associated pathways, such as MAPK/RTK, Ras, and PI3K-Akt signaling pathways. In summary, our observations demonstrate that the novel miRNA-based OS and RFS signatures are independent prognostic indicators for BC patients and worthy to be validated by further prospective studies.

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Section: Discussionmentioning

confidence: 99%

Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer

Tang

Zeng³

et al. 2019

Disease Markers

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“…MiR-29b-1-5p is downregulated in human BRCA1-associated BC, and BRCA1 impacts miR-29b-1-5p expression in BC cell lines, probably using promoter binding and transcriptional regulation. MiR-29b-1-5p, miR-664, miR-16-2, and miR-744 represent significant biomarkers for stratification of OS versus generally utilized clinical biomarkers such as lymph-node status and age at diagnosis in TNBC patients [92].…”

Section: Main Mirnas and Biology Of Tnbc With Basal-like Phenotypementioning

confidence: 99%

Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype

Angius

Cossu-Rocca

Arru

et al. 2020

Cancers

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Development of new research, classification, and therapeutic options are urgently required due to the fact that TNBC is a heterogeneous malignancy. The expression of high molecular weight cytokeratins identifies a biologically and clinically distinct subgroup of TNBCs with a basal-like phenotype, representing about 75% of TNBCs, while the remaining 25% includes all other intrinsic subtypes. The triple negative phenotype in basal-like breast cancer (BLBC) makes it unresponsive to endocrine therapy, i.e., tamoxifen, aromatase inhibitors, and/or anti-HER2-targeted therapies; for this reason, only chemotherapy can be considered an approach available for systemic treatment even if it shows poor prognosis. Therefore, treatment for these subgroups of patients is a strong challenge for oncologists due to disease heterogeneity and the absence of unambiguous molecular targets. Dysregulation of the cellular miRNAome has been related to huge cellular process deregulations underlying human malignancy. Consequently, epigenetics is a field of great promise in cancer research. Increasing evidence suggests that specific miRNA clusters/signatures might be of clinical utility in TNBCs with basal-like phenotype. The epigenetic mechanisms behind tumorigenesis enable progress in the treatment, diagnosis, and prevention of cancer. This review intends to summarize the epigenetic findings related to miRNAome in TNBCs with basal-like phenotype.

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“…The miR-29b-1-5p molecule represents the 5′-miRNA generated from the same stem-loop as the 3′ miRNA, designated miR-29b-1 , and the sequence encoding miR-29 resides within 7q32.3 locus of the human genome [7,8]. The mechanism of transcriptional regulation of miR-29b-1-5p is identical to that of miR-29b-1 , although they differ with respect to their processing and maturation [8]. Evidence indicates that miR-29b-1 acts as a tumor suppressor in many malignancies [9].…”

Section: Introductionmentioning

confidence: 99%

“…For example, expression of miR-29b-1-5p is significantly diminished in sunitinib-resistant renal carcinoma cells (RCCs) [10]. Further, miR-29b-1-5p is downregulated in basal-like and triple-negative breast cancers [8,11]. Conversely, higher levels of expression of miR-29b-1-5p are associated with the proliferation of bladder cancer cells [12], and overexpression of miR-29b-1-5p contributes to the development of gastric cancers from premalignant adenomas [13].…”

Section: Introductionmentioning

confidence: 99%

The Oncogenic Activity of miR-29b-1-5p Induces the Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

Kurihara‐Shimomura

Sasahira

Shimomura

et al. 2019

JCM

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Background: The relationship between miR-29b-1-5p and c-Met proto-oncogene in oral squamous cell carcinoma (OSCC) remains to be investigated. This study aimed to reveal the role of miR-29b-1-5p in the pathogenesis of OSCC using molecular and biological analyses. Methods: We investigated the expression of miR-29b-1-5p, c-Met, and markers of the epithelial-mesenchymal transition (EMT) in the tissues of 49 patients with OSCC and in human OSCC cells with different tumorigenicity. Further, we determined the effects of miR-29b-1-5p on the phenotypes of OSCC cell lines. Results: The expression levels of miR-29b-1-5p in most patients with OSCC were higher than those of the normal oral epithelium. In OSCC, upregulation of miR-29b-1-5p significantly correlated with histological grade, the EMT, and the immunohistochemical grade, indicated by c-Met expression. The prognosis was poor for patients with miR-29b-1-5p expression and coexpression of miR-29b-1-5p and c-Met. In OSCC cells exhibiting the EMT phenotype, knockdown of miR-29b-1-5p suppressed the EMT, which was recovered by enforced expression of c-Met. Further, the mRNA encoding cadherin 1 (CDH1) was a direct target of miR-29b-1-5p. Conclusions: Our results suggest that miR-29b-1-5p acts as an oncogenic miRNA that synergizes with c-Met to induce the EMT of OSCC cells.

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MiR-29b-1-5p is altered in BRCA1 mutant tumours and is a biomarker in basal-like breast cancer

Cited by 17 publications

References 53 publications

Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer

Identification of miRNA-Based Signature as a Novel Potential Prognostic Biomarker in Patients with Breast Cancer

Modulatory Role of microRNAs in Triple Negative Breast Cancer with Basal-Like Phenotype

The Oncogenic Activity of miR-29b-1-5p Induces the Epithelial-Mesenchymal Transition in Oral Squamous Cell Carcinoma

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