Dataset Information

MicroRNA-4417 is a tumor suppressor and prognostic biomarker for triple-negative breast cancer.

ABSTRACT: Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer with poor prognosis due to lack of druggable targets such as hormone and growth factor receptors. Therefore, identification of targetable regulators such as miRNAs could provide new avenues for therapeutic applications. Here, we report that the expression of miR-4417 is suppressed during the progression of TNBC cells from non-malignant to the malignant stage. MiR-4417 is localized to chromosome 1p36, a region with high frequency of loss of heterozygosity in multiple cancers, and its biogenesis is DICER-dependent. Low expression of miR-4417 is significantly associated with worse prognosis in TNBC patients, while overexpression of miR-4417 is sufficient to inhibit migration and mammosphere formation of TNBC cells in vitro. Overall, our findings suggest miR-4417 exerts a tumor suppressive effect and thereby could serve as a prognostic biomarker and therapeutic tool against TNBC.

SUBMITTER: Wong CK

PROVIDER: S-EPMC6605987 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

MicroRNA-4417 is a tumor suppressor and prognostic biomarker for triple-negative breast cancer.

Wong Chen Khuan CK Gromisch Christopher C Ozturk Sait S Papageorgis Panagiotis P Abdolmaleky Hamid Mostafavi HM Reinhard Björn M BM Thiagalingam Arunthathi A Thiagalingam Sam S

Cancer biology & therapy 20190328 8

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer with poor prognosis due to lack of druggable targets such as hormone and growth factor receptors. Therefore, identification of targetable regulators such as miRNAs could provide new avenues for therapeutic applications. Here, we report that the expression of miR-4417 is suppressed during the progression of TNBC cells from non-malignant to the malignant stage. MiR-4417 is localized to chromosome 1p36, a region with ...[more]

PMID: 30922194

Similar Datasets

Project description:BackgroundThe clinical outcome of triple-negative breast cancer (TNBC) is poor. Finding more targets for the treatment of TNBC is an urgent need. SENPs are SUMO-specific proteins that play an important role in SUMO modification. Among several tumor types, SENPs have been identified as relevant biomarkers for progression and prognosis. The role of SENPs in TNBC is not yet clear.MethodsThe expression and prognosis of SENPs in TNBC were analyzed by TCGA and GEO data. SENP3 coexpression regulatory networks were determined by weighted gene coexpression network analysis (WGCNA). Least absolute shrinkage and selection operator (LASSO) and Cox univariate analyses were used to develop a risk signature based on genes associated with SENP3. A time-dependent receiver operating characteristic (ROC) analysis was employed to evaluate a risk signature's predictive accuracy and sensitivity. Moreover, a nomogram was constructed to facilitate clinical application.ResultsThe prognostic and expression effects of SENP family genes were validated using the TCGA and GEO databases. SENP3 was found to be the only gene in the SENP family that was highly expressed and associated with an unfavorable prognosis in TNBC patients. Cell functional experiments showed that knockdown of SENP3 leads to growth, invasion, and migration inhibition of TNBC cells in vitro. By using WGCNA, 273 SENP3-related genes were identified. Finally, 11 SENP3-related genes were obtained from Cox univariate analysis and LASSO regression. Based on this, a prognostic risk prediction model was established. The risk signature of SENP3-related genes was verified as an independent prognostic marker for TNBC patients.ConclusionAmong SENP family genes, we found that SENP3 was overexpressed in TNBC and associated with a worse prognosis. SENP3 knockdown can inhibit tumor proliferation, invasion, and migration. In TNBC patients, a risk signature based on the expression of 11 SENP3-related genes may improve prognosis prediction. The established risk markers may be promising prognostic biomarkers that can guide the individualized treatment of TNBC patients.

Project description:BackgroundThe study assessed the epigenetic regulation and the role of microRNA (miR) expression in locally advanced triple negative breast cancers (TNBC) and comparison with the clinico-pathological variables and survival.MethodsFifty patients of locally advanced TNBC during the period 2011-2013 were included. Expression level of test microRNA (miR-182 and miR-18a) was determined using Taqman quantitative Real time polymerase chain reaction (qRT-PCR) from formalin fixed paraffin embedded biopsy blocks. Clinical and demographic information and survival data was retrieved from the Hospital medical records.ResultsAn improved clinical complete response (cCR) was observed in patients with age ≥ 45 years (80%), premenopausal status (70%), tumor size < 6 cms (80%), nodal status N0-N1 (95%) and grade II-III tumor (80%). A statistically significant correlation was observed on comparison of cCR with menopausal status (p-value 0.020), T category (p-value 0.018) and the clinical nodal status (p-value 0.003). pCR also correlated with clinical nodal status (p-value 0.008). Epigenetically, miR-18a under expression (< 8.84) was most commonly associated with tumor size < 6 cms (76.7%), clinical nodal status N0-N1 (90%), cCR (60%) and pCR (53.3%). A similar trend was observed with miR-182. Statistical significance was observed with T category (p-values 0.003 and 0.004), clinical nodal status (p-values 0.001 and 0.001), clinical response (p-values 0.002 and 0.002) and pathological response (p-values 0.007 and 0.006) with respect to miR-18a and miR-182, respectively. Also, the menopausal status significantly correlated with the miR-182 expression (p-value 0.009). miR-182 overexpression (≥ 6.32) was not observed in any of the postmenopausal patients. A univariate cox proportional hazard regression model also showed statistical interactions (p-values <0.004).ConclusionmiR-182 and miR-18a overexpression correlates with worse clinical and pathological tumor characteristics in locally advanced TNBC and hence could be used to predict the outcomes and prognosis in these patients.

Dataset Information

MicroRNA-4417 is a tumor suppressor and prognostic biomarker for triple-negative breast cancer.

Publications

MicroRNA-4417 is a tumor suppressor and prognostic biomarker for triple-negative breast cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets