Prognostic and Functional Significant of Heat Shock Proteins (HSPs) in Breast Cancer Unveiled by Multi-Omics Approaches

Buttacavoli, Miriam; Cara, Gianluca Di; D’Amico, Cesare; Geraci, Fabiana; Pucci‐Minafra, Ida; Feo, Salvatore

doi:10.3390/biology10030247

Cited by 13 publications

(26 citation statements)

References 73 publications

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“…HSPs have been reported as biomarkers and potential drug targets of cancers for decades. A recent integrative analysis of multi-omics data uncovered the distinct impact of several HSPs (including DNAJB4) members in BRCA progression [40]. Our study discovered that DNAJB4 could act as a prognostic marker in UCEC.…”

Section: Discussionmentioning

confidence: 59%

Identifying Complex lncRNA/Pseudogene-miRNA-mRNA Crosstalk in Hormone-Dependent Cancers

Jayarathna¹,

Rentería²,

Sauret³

et al. 2021

Preprint

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The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that not only messenger RNAs but also other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long non-coding RNAs-associated ceRNA networks. Here, we identify an extended-ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of four hormone-dependent (HD) cancers, i.e., prostate, breast, colorectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across four HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding shared molecular pathogenesis in a group of related diseases.

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Section: Discussionmentioning

confidence: 59%

Identifying Complex lncRNA/Pseudogene-miRNA-mRNA Crosstalk in Hormone-Dependent Cancers

Jayarathna¹,

Rentería²,

Sauret³

et al. 2021

Preprint

View full text Add to dashboard Cite

show abstract

“…HSPs have been reported as biomarkers and potential drug targets of cancers for decades. A recent integrative analysis of multi-omics data uncovered the distinct impact of several HSP (including DNAJB4) members on BRCA progression [40]. Our study discovered that DNAJB4 could act as a prognostic marker in UCEC.…”

Section: Discussionmentioning

confidence: 60%

Identifying Complex lncRNA/Pseudogene–miRNA–mRNA Crosstalk in Hormone-Dependent Cancers

Jayarathna

Rentería

Sauret

et al. 2021

Biology

View full text Add to dashboard Cite

The discovery of microRNAs (miRNAs) has fundamentally transformed our understanding of gene regulation. The competing endogenous RNA (ceRNA) hypothesis postulates that messenger RNAs and other RNA transcripts, such as long non-coding RNAs and pseudogenes, can act as natural miRNA sponges. These RNAs influence each other’s expression levels by competing for the same pool of miRNAs through miRNA response elements on their target transcripts, thereby modulating gene expression and protein activity. In recent years, these ceRNA regulatory networks have gained considerable attention in cancer research. Several studies have identified cancer-specific ceRNA networks. Nevertheless, prior bioinformatic analyses have focused on long-non-coding RNA-associated ceRNA networks. Here, we identify an extended ceRNA network (including both long non-coding RNAs and pseudogenes) shared across a group of five hormone-dependent (HD) cancers, i.e., prostate, breast, colon, rectal, and endometrial cancers, using data from The Cancer Genome Atlas (TCGA). We performed a functional enrichment analysis for differentially expressed genes in the shared ceRNA network of HD cancers, followed by a survival analysis to determine their prognostic ability. We identified two long non-coding RNAs, nine genes, and seventy-four miRNAs in the shared ceRNA network across five HD cancers. Among them, two genes and forty-one miRNAs were associated with at least one HD cancer survival. This study is the first to investigate pseudogene-associated ceRNAs across a group of related cancers and highlights the value of this approach to understanding the shared molecular pathogenesis in a group of related diseases.

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“…Complex I-related proteins ( NDUFA2 ) and UBE2C -encoded protein are discussed in Section 2.3.1 . DnaJ homologue subfamily C member 11 is a heat shock protein, recently found to be upregulated in breast cancers such as basal, luminal B, and HER2 breast cancer subtypes, and downregulated in other tumour types; however, its functional role in breast cancer has not yet been deciphered [ 113 , 114 ].…”

Section: Resultsmentioning

confidence: 99%

Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

Alsherbiny

Bhuyan

Low

et al. 2021

IJMS

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Cannabidiol (CBD), a nonpsychoactive phytocannabinoid, has recently emerged as a potential cytotoxic agent in addition to its ameliorative activity in chemotherapy-associated side effects. In this work, the potential interactions of CBD with docetaxel (DOC), doxorubicin (DOX), paclitaxel (PTX), vinorelbine (VIN), and 7-ethyl-10-hydroxycamptothecin (SN−38) were explored in MCF7 breast adenocarcinoma cells using different synergy quantification models. The apoptotic profiles of MCF7 cells after the treatments were assessed via flow cytometry. The molecular mechanisms of CBD and the most promising combinations were investigated via label-free quantification proteomics. A strong synergy was observed across all synergy models at different molar ratios of CBD in combination with SN−38 and VIN. Intriguingly, synergy was observed for CBD with all chemotherapeutic drugs at a molar ratio of 636:1 in almost all synergy models. However, discording synergy trends warranted the validation of the selected combinations against different models. Enhanced apoptosis was observed for all synergistic CBD combinations compared to monotherapies or negative controls. A shotgun proteomics study highlighted 121 dysregulated proteins in CBD-treated MCF7 cells compared to the negative controls. We reported the inhibition of topoisomerase II β and α, cullin 1, V-type proton ATPase, and CDK-6 in CBD-treated MCF7 cells for the first time as additional cytotoxic mechanisms of CBD, alongside sabotaged energy production and reduced mitochondrial translation. We observed 91 significantly dysregulated proteins in MCF7 cells treated with the synergistic combination of CBD with SN−38 (CSN−38), compared to the monotherapies. Regulation of telomerase, cell cycle, topoisomerase I, EGFR1, protein metabolism, TP53 regulation of DNA repair, death receptor signalling, and RHO GTPase signalling pathways contributed to the proteome-wide synergistic molecular mechanisms of CSN−38. In conclusion, we identified significant synergistic interactions between CBD and the five important chemotherapeutic drugs and the key molecular pathways of the combination of CBD and CSN−38 in MCF7 cells. Further in vivo and clinical studies are warranted to evaluate the implementation of CBD-based synergistic adjuvant therapies for breast cancer.

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Prognostic and Functional Significant of Heat Shock Proteins (HSPs) in Breast Cancer Unveiled by Multi-Omics Approaches

Cited by 13 publications

References 73 publications

Identifying Complex lncRNA/Pseudogene-miRNA-mRNA Crosstalk in Hormone-Dependent Cancers

Identifying Complex lncRNA/Pseudogene-miRNA-mRNA Crosstalk in Hormone-Dependent Cancers

Identifying Complex lncRNA/Pseudogene–miRNA–mRNA Crosstalk in Hormone-Dependent Cancers

Synergistic Interactions of Cannabidiol with Chemotherapeutic Drugs in MCF7 Cells: Mode of Interaction and Proteomics Analysis of Mechanisms

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