Biology subjects

Rusetska, N.

Publications and source records attributed to Rusetska, N..

3 recordsLinked to original sources

bioRxiv2026

Coordinated alterations in SWI/SNF chromatin remodeling complex, mRNA splicing and mRNA methylation as hallmarks of salivary gland adenoid cystic carcinoma (SACC)

Salivary gland adenoid cystic carcinoma (SACC) is a rare, poorly understood malignancy. Here, using spatial transcriptomics, we show that disturbances in epigenetic regulation including chromatin remodeling, epitranscriptomic control by m6A RNA methylation, and RNA splicing may contribute to SACC. We demonstrated that machineries responsible for these processes-SWI/SNF chromatin remodeling complex (CRC), NineTeen Complex (NTC), and m6A RNA methylation complex interact directly. Immunohistochemistry on 48 SACC tumor samples indicated altered abundance of METTL3, METTL14, WTAP (m6A RNA methylation) and PRP19, CDC5L, PLRG1 (NTC-splicing) proteins. Chromatin immunoprecipitation indicated direct regulation of genes encoding subunits of SWI/SNF, NTC and RNA methylation complexes, and some EMT (epithelial-to-mesenchymal) marker genes by BRM (BRAHMA). Transcriptomic re-analysis revealed broad alterations in transcript usage, and splicing events in SACC. Collectively, our findings provide the first evidence that coordinated disruption of chromatin remodeling, RNA methylation, and splicing contributes to SACC development and progression, highlighting new avenues for therapeutic exploration.

cancer biology↗

bioRxiv2025

Renal cancer cell-derived amphiregulin recruits mesenchymal stromal cells, induces their glycolytic switch, and promotes tumour growth

Mesenchymal stem/stromal cells (MSCs) are multipotent cells that support wound healing. Tumours, often called as wounds that do not heal, recruit MSCs, which in turn support tumour growth. The immunomodulatory MSCs properties are facilitated under hypoxic conditions, while tumours are often hypoxic and immune-suppressed. It is unclear how MSCs wound healing actions are prevented in tumours. Here, we found that renal cancer cells secrete amphiregulin which induces MSCs recruitment and facilitates tumour growth in vivo. In MSCs, AREG triggers HIF1A degradation and transcriptional reprogramming, leading to glycolytic switch, increased migration and attenuation of immunoregulatory profile. In renal cancer cells, AREG stimulates expression of oncogenic proteins, including AKR1C3, leading to increased tumour growth and angiogenesis. To our knowledge, this is the first study showing that glycolytic switch in MSCs is induced by cancer. Our study provides insight into how renal cancer cells attenuate MSCs wound pro-healing properties to facilitate tumour growth.

cancer biology↗

bioRxiv2022

Transcriptomic classification of pituitary neuroendocrine tumors causing acromegaly

Acromegaly results from growth hormone hypersecretion caused by somatotroph pituitary neuroendocrine tumor (PitNET). Our molecular profiling revealed that acromegaly-causing tumors form three distinct transcriptomic subgroups with different histological/clinical features. Transcriptomic subtypes of somatotroph tumors differ in the expression levels of numerous genes including those involved in hormone secretion and genes with known prognostic value. They can be distinguished by determining the expression of marker genes. Transcriptomic group 1 includes [~]20% of acromegaly patients with GNAS mutations-negative, mainly densely granulated tumors with NR5A1 (SF-1) and GIPR co-expression. Group 2 tumors are the most common (46%) and include mainly GNAS-mutated, densely granulated somatotroph and mixed PitNETs. They have significantly smaller size and express favorable prognosis-related genes. Group 3 includes predominantly sparsely granulated somatotroph PitNETs with low GNAS mutations frequency causing [~]35% of acromegaly cases. Ghrelin signaling is implied in their pathogenic mechanism, they have unfavorable gene expression profile, and invasive growth rate. Since a subgroup of somatotroph tumors have high NR5A1 expression, using SF-1 as classification marker specific to gonadotroph PitNETs could be reconsidered.

cancer biology↗