Expression Profile of Inflammatory Breast Cancer

Shkurnikov, M. Yu.; Nechaev, I. N.; Khaustova, N. A.; Krainova, N. A.; Savelov, N.; Grinevich, V. N.; Saribekyan, E. K.

doi:10.1007/s10517-013-2221-2

Cited by 6 publications

(1 citation statement)

References 15 publications

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“…Interestingly, gene variant located in a vicinity of SORCS2 (rs4234798) demonstrated genome-wide significant associations with circulating concentrations of IGFBP-3 and IGF-I (Kaplan et al, 2011; Teumer et al, 2016), previously described as a prognostic marker in basal-like triple-negative breast cancer (Marzec et al, 2015; Julovi et al, 2018), and as a part of 19-gene expression signature which substantially outperforms Dukes' classification predicting the survival of patients with colorectal cancer (Aziz et al, 2016). Protein encoded by SORCS2 gene coordinates intracellular transport of the glutamate and cysteine transporter EAAT3 (Malik et al, 2019) in the neurons, where it provides a degree of protection from oxidative stress and epilepsy-induced cell death (Shkurnikov et al, 2013). Given that expression of SORCS2 mRNA is highly restricted to the nervous system and the kidneys, it is tempting to speculate that the function of relatively high levels of SORCS2 expression observed in basal-like breast carcinomas should be attributed to intragenic miRNA hsa-miR-4274.…”

Section: Discussionmentioning

confidence: 99%

LAMA4-Regulating miR-4274 and Its Host Gene SORCS2 Play a Role in IGFBP6-Dependent Effects on Phenotype of Basal-Like Breast Cancer

Shkurnikov

Никулин

Nersisyan

et al. 2019

Front. Mol. Biosci.

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Specificity of RNAi to selected target is challenged by off-target effects, both canonical and non-canonical. Notably, more than half of all human microRNAs are co-expressed with hosting them proteincoding genes. Here we dissect regulatory subnetwork centered on IGFBP6 gene, which is associated with low proliferative state and high migratory activity of basal-like breast cancer. We inhibited expression of IGFBP6 gene in a model cell line for basal-like breast carcinoma MDA-MB-231, then traced secondary and tertiary effects of this knockdown to LAMA4, a laminin encoding gene that contributes to the phenotype of triple-negative breast cancer. LAMA4-regulating miRNA miR-4274 and its host gene SORCS2 were highlighted as intermediate regulators of the expression levels of LAMA4, which correlated in a basal-like breast carcinoma sample subset of TCGA to the levels of SORCS2 negatively. Overall, our study points that the secondary and tertiary layers of regulatory interactions are certainly underappreciated. As these types of molecular event may significantly contribute to the formation of the cell phenotypes after RNA interference based knockdowns, further studies of multilayered molecular networks affected by RNAi are warranted.

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Section: Discussionmentioning

confidence: 99%

LAMA4-Regulating miR-4274 and Its Host Gene SORCS2 Play a Role in IGFBP6-Dependent Effects on Phenotype of Basal-Like Breast Cancer

Shkurnikov

Никулин

Nersisyan

et al. 2019

Front. Mol. Biosci.

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Potentialities of MicroRNA Diagnosis in Patients with Bladder Cancer

Shegay

Zhavoronkov²,

Гайфуллин

et al. 2017

Bull Exp Biol Med

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Despite promising vista of the use of microRNA in molecular diagnosis of bladder cancer, there are few data on their expression profiles, which impedes assessment of diagnostic value of these marker molecules. In this study, suppression subtractive hybridization, on-chip hybridization, and high-throughput deep sequencing focused on profiling microRNA and assessing the diagnostic value of revealed marker molecules.

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Path to drugging functional clones of luminal breast cancers using in-depth proteomics with spatially resolved mass spectrometry guided by MALDI imaging

Hajjaji

Aboulouard

Cardon

et al. 2021

Preprint

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Integrating tumor heterogeneity in the drug discovery process is a key challenge to tackle breast cancer resistance. Identifying protein targets for functionally distinct tumor clones is particularly important to tailor therapy to the heterogeneous tumor subpopulations. For this purpose, we performed an unsupervised, label-free, spatially resolved shotgun proteogenomic guided by MALDI mass spectrometry imaging (MSI) on 124 selected tumor clonal areas from early luminal breast cancers, tumor stroma, and breast cancer metastases. 2868 proteins were identified. The main protein classes found in the clonal proteome dataset were enzymes, cytoskeletal proteins, membrane-traffic, translational or scaffold proteins, or transporters. As a comparison, gene-specific transcriptional regulators, chromatin related proteins or transmembrane signal receptor were more abundant in the TCGA dataset. Moreover, 26 mutated proteins have been identified. Similarly, expanding the search to alternative proteins databases retrieved 126 alternative proteins in the clonal proteome dataset. The majority of these alternative proteins were coded mainly from non-coding RNA. To fully understand the molecular information brought by our approach and its relevance to drug target discovery, the clonal proteomic dataset was further compared to the TCGA breast cancer database and two transcriptomic panels, BC360 (nanoString) and CDx (Foundation One). We retrieved 139 pathways in the clonal proteome dataset. Only 55% of these pathways were also present in the TCGA dataset, 68% in BC360 and 50% in CDx. Seven of these pathways have been suggested as candidate for drug targeting, 22 have been associated with breast cancer in experimental or clinical reports, the remaining 19 pathways have been understudied in breast cancer. Among the anticancer drugs, 35 drugs matched uniquely with the clonal proteome dataset, with only 7 of them already approved in breast cancer. The number of target and drug interactions with non-anticancer drugs (such as agents targeting the cardiovascular system, metabolism, the musculoskeletal or the nervous systems) was higher in the clonal proteome dataset (540 interactions) compared to TCGA (83 interactions), BC360 (419 interactions), or CDx (172 interactions). Thus, we described the non-redundant knowledge brought by this approach compared to TCGA or transcriptomic panels, the targetable proteins identified in the clonal proteome dataset, and the potential of this approach for drug discovery and repurposing through drug interactions with antineoplastic agents and non-anticancer drugs.

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Expression Profile of Inflammatory Breast Cancer

Cited by 6 publications

References 15 publications

LAMA4-Regulating miR-4274 and Its Host Gene SORCS2 Play a Role in IGFBP6-Dependent Effects on Phenotype of Basal-Like Breast Cancer

LAMA4-Regulating miR-4274 and Its Host Gene SORCS2 Play a Role in IGFBP6-Dependent Effects on Phenotype of Basal-Like Breast Cancer

Potentialities of MicroRNA Diagnosis in Patients with Bladder Cancer

Path to drugging functional clones of luminal breast cancers using in-depth proteomics with spatially resolved mass spectrometry guided by MALDI imaging

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