The synergistic effect of CDKN2B-AS1 and SPC25 on triple-negative breast cancer

Abstract

Background: Accumulating evidence suggests that long non-coding ribonucleic acid (RNA) cyclindependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) and messenger RNA (mRNA) spindle component 25 (SPC25) contribute to tumorigenesis and progression in various cancers. However, the synergistic effect between CDKN2B-AS1 and SPC25 has not yet been fully elucidated in triple-negative breast cancer (TNBC). This study sought to examine the synergistic effect of CDKN2B-AS1 and SPC25 and uncover a novel mechanism for the progression of TNBC. Methods:The transcriptome profiles of TNBC in The Cancer Genome Atlas (TCGA) were calculated for differentially expressed genes (DEGs). Gene co-expression networks were constructed via a weighted correlation network analysis. We validated the relationship between CDKN2B-AS1 and SPC25 by bioinformatics and in-vitro studies (including Cell Counting Kit-8, transwell assays, and quantitative realtime polymerase chain reaction).Results: CDKN2B-AS1 was found to be carcinogenic and was significantly upregulated and co-expressed with elevated SPC25 expression levels in the TNBC cells and sequencing profiles. Notably, the SPC25 mRNA levels were associated with poor clinical outcomes in TNBC patients. Specifically, the knockdown of CDKN2B-AS1 significantly inhibited TNBC cell proliferation and migration. Conclusions:We identified a novel cancer-promoting regulation axis. The co-expression of CDKN2B-AS1 and SPC25 is expected to serve as a powerful candidate biomarker for diagnostic and prognostic purposes in TNBC.

Network-based approach elucidates critical genes in BRCA subtypes and chemotherapy response in triple negative breast cancer

“… 51 , 52 Gong et al. classified the TNBC samples into 3 categories based on their metabolic features and their further analysis reveals that inhibiting lactate dehydrogenase could enhance the response to anti-PD1 immunotherapy 53 and lastly, M subtype was associated with protein modification (protein autophosphorylation and peptidyl-threonine modification), signaling (GPCR signaling pathway, mitotic spindle checkpoint signaling), and negative regulation of nuclear division 54 , 55 , 56 ( Figures 6 B–6E). Complete lists of the enriched common and unique processes in each subtype are provided in the Tables S72–S75 .…”

Network-based approach elucidates critical genes in BRCA subtypes and chemotherapy response in Triple Negative Breast Cancer

“…For the activated TopNets, 5 genes --FOXA1, CTNNB1, JUN, FOS and ALB were found in all TNBC subtypes and 49, 55, 61 and 48 genes were unique to BL1, BL2, LAR and M subtypes respectively. Common genes were broadly associated with developmental processes (Figure 8A & Supplementary Table S41); BL1 subtype was enriched mainly for hemostasis and coagulation processes [34][35][36] ; BL2 subtype for chemotaxis and signaling processes 37,38 ; LAR subtype for metabolic process 39,40 and lastly M subtype was associated with modification and nuclear division processes [41][42][43] (Figure 8B-E). Detailed discussion of the processes associated with TNBC subtype-specific mediators of resistance, and their functional relevance is discussed in Supplementary Note 1.…”