Identification of therapeutic targets and prognostic biomarkers from the hnRNP family in invasive breast carcinoma

Abstract

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are RNA-binding proteins that are reported to play a crucial role in the pathogenic process of multiple malignancies. However, their expression patterns, clinical application significance and prognostic values in invasive breast carcinoma (BRCA) remain unknown. In this study, we investigated hnRNP family members in BRCA using accumulated data from Oncomine 4.5, UALCAN Web portal and other available databases. We explored the expression and prognostic value level of hnRNPs in BRCA. We further analyzed their association with the clinicopathological features of BRCA patients. Subsequently, we calculated the alteration frequency of hnRNPs, constructed the interaction network of hnRNPs, and examined the potential coexpression genes of hnRNPs, revealing that HNRNPU and SYNCRIP are the core molecular genes requiring further investigation for BRCA. We validated the immunohistochemistry (IHC) pattern to simulate clinical applications based on pathology. Cell function experiments conducted in vitro indicated that HNRNPU can promote epithelial-mesenchymal transition, functionally stimulating the invasion capacity and inhibiting the viability of invasive BRCA cells. In summary, our systematic analysis demonstrated that HNRNPU was the key molecule that played a fundamental role in BRCA metastasis, which may facilitate the development of new diagnostic and prognostic markers for the analysis of BRCA progression.

High expression of RUVBL1 and HNRNPU is associated with poor overall survival in stage I and II non-small cell lung cancer patients

“…It controls various cell functions such as transcription, nuclear chromatin organization, alternative pre-mRNA splicing, telomere-length regulation, inhibition of apoptosis, angiogenesis, or cell invasion [ 8 – 10 ]. Mounting evidence suggests that HNRNP family members play an essential role in numerous cancers, including breast cancer, ovarian cancer, hepatocellular cancer, melanoma, bladder cancer, prostate cancer and pancreatic cancer [ 11 – 14 ].…”

CDC20-Mediated hnRNPU Ubiquitination Regulates Chromatin Condensation and Anti-Cancer Drug Response

“…As previously described, hnRNPU plays a critical role in regulating chromatin dynamics through functional interaction with cohesion complex and chromatin loop formation [ 32 , 33 ]. Dysregulation of hnRNPU results in carcinogenesis and drug resistance [ 34 , 35 , 42 ]. Co-immunoprecipitation assays performed in MDA-MB-468 cells confirmed the interaction between endogenous CDC20 and hnRNPU ( Figure 3 f).…”

“…Moreover, hnRNPU expression was associated with cisplatin sensitivity in bladder cancer [ 42 ]. Additionally, hnRNPU has been shown to promote breast cancer cell proliferation, migration, and invasion [ 35 ]. CTCF can also affect breast cancer development by regulating target genes [ 63 ].…”

“…Song et al showed that binding of long noncoding RNA HNF4A-AS1 to the RGG domain of hnRNPU facilitates hnRNPU–CTCF interaction leading to CTCF transactivation and subsequent transcriptional alteration of HNF4A and other cancer-associated genes in neuroblastoma (NB) cells [ 34 ]. Moreover, hnRNPU promotes breast cancer cell proliferation, migration, and invasion [ 35 ]. Therefore, investigation of hnRNPU regulation in breast cancer circumstances and the development of related targeting strategies could lead to a new anticancer therapy.…”

Genomic analyses identify biological processes of miR-125 mediated breast cancer cells

“…Interestingly, calreticulin has been found to interact with several GPCR proteins such as AT1R and V2R 44 . Jiawei Zhou et al found HNRNPU enhances epithelial-mesenchymal transition, invasion capacity but represses the viability of invasive breast carcinoma cells 45 . Circadian gene clocks and their target genes are involved in a number of cell functions including proliferation, differentiation, metabolism, migration, and secretion 46-50 .…”