Integrative Transcriptome-Wide Analyses Uncover Novel Risk-Associated MicroRNAs in Hormone-Dependent Cancers

Jayarathna, Dulari; Rentería, Miguel E.; Malik, Adil; Sauret, Emilie; Batra, Jyotsna; Gandhi, Neha S.

doi:10.3389/fgene.2021.716236

Cited by 5 publications

(3 citation statements)

References 58 publications

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“…Among these four miRNAs, Tuersong et al 3 have demonstrated that hsa-miR-204 was downregulated and hsa-miR-301b was upregulated in patients with BRCA compared with healthy controls and were associated with overall survival. Our previous transcriptome-wide association study also demonstrated hsa-miR-204 as a tumour-suppressive miRNA in prostate cancer with statistically significant low expressed levels in prostate cancer cell lines 50 . Moreover, we found two genes, SPRY2 and CHL1 , involved in Tuersong et al 3 and our works ( SPRY2 in stages I–IV and CHL1 in stages II, III, and IV).…”

Section: Discussionmentioning

confidence: 73%

Integrative competing endogenous RNA network analyses identify novel lncRNA and genes implicated in metastatic breast cancer

Jayarathna

Rentería

Batra

et al. 2023

Sci Rep

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Competing endogenous RNAs (ceRNAs) have gained attention in cancer research owing to their involvement in microRNA-mediated gene regulation. Previous studies have identified ceRNA networks of individual cancers. Nevertheless, none of these studies has investigated different cancer stages. We identify stage-specific ceRNAs in breast cancer using the cancer genome atlas data. Moreover, we investigate the molecular functions and prognostic ability of ceRNAs involved in stage I–IV networks. We identified differentially expressed candidate ceRNAs using edgeR and limma R packages. A three-step analysis was used to identify statistically significant ceRNAs of each stage. Survival analysis and functional enrichment analysis were conducted to identify molecular functions and prognostic ability. We found five genes and one long non-coding RNA unique to the stage IV ceRNA network. These genes have been described in previous breast cancer studies. Genes acted as ceRNAs are enriched in cancer-associated pathways. Two, three, and three microRNAs from stages I, II, and III were prognostic from the Kaplan–Meier survival analysis. Our results reveal a set of unique ceRNAs in metastatic breast cancer. Further experimental work is required to evaluate their role in metastasis. Moreover, identifying stage-specific ceRNAs will improve the understanding of personalised therapeutics in breast cancer.

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Section: Discussionmentioning

confidence: 73%

Integrative competing endogenous RNA network analyses identify novel lncRNA and genes implicated in metastatic breast cancer

Jayarathna

Rentería

Batra

et al. 2023

Sci Rep

Self Cite

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“…Several characteristics, such as expression signatures, DNA mismatch repair deficiency (MMR-D), and BRCA1 status, are currently used agnostically regardless of cancer origin ( 22 , 98 , 99 ). Breast cancer and PCa are both proposed to be biologically related ( 100 , 101 ), and both tumors share common biological features during hormone-dependent development ( 23 , 29 ). Multi-omics studies in breast and prostate cancer identified common epigenome alterations in CpG islands in predicted therapeutic targets.…”

Section: Discussionmentioning

confidence: 99%

Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence

Lautert-Dutra,

Melo,

Chaves

et al. 2023

Front. Oncol.

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The diverse clinical outcomes of prostate cancer have led to the development of gene signature assays predicting disease progression. Improved prostate cancer progression biomarkers are needed as current RNA biomarker tests have varying success for intermediate prostate cancer. Interest grows in universal gene signatures for invasive carcinoma progression. Early breast and prostate cancers share characteristics, including hormone dependence and BRCA1/2 mutations. Given the similarities in the pathobiology of breast and prostate cancer, we utilized the NanoString BC360 panel, comprising the validated PAM50 classifier and pathway-specific signatures associated with general tumor progression as well as breast cancer-specific classifiers. This retrospective cohort of primary prostate cancers (n=53) was stratified according to biochemical recurrence (BCR) status and the CAPRA-S to identify genes related to high-risk disease. Two public cohort (TCGA-PRAD and GSE54460) were used to validate the results. Expression profiling of our cohort uncovered associations between PIP and INHBA with BCR and high CAPRA-S score, as well as associations between VCAN, SFRP2, and THBS4 and BCR. Despite low levels of the ESR1 gene compared to AR, we found strong expression of the ER signaling signature, suggesting that BCR may be driven by ER-mediated pathways. Kaplan-Meier and univariate Cox proportional hazards regression analysis indicated the expression of ESR1, PGR, VCAN, and SFRP2 could predict the occurrence of relapse events. This is in keeping with the pathways represented by these genes which contribute to angiogenesis and the epithelial-mesenchymal transition. It is likely that VCAN works by activating the stroma and remodeling the tumor microenvironment. Additionally, SFRP2 overexpression has been associated with increased tumor size and reduced survival rates in breast cancer and among prostate cancer patients who experienced BCR. ESR1 influences disease progression by activating stroma, stimulating stem/progenitor prostate cancer, and inducing TGF-β. Estrogen signaling may therefore serve as a surrogate to AR signaling during progression and in hormone-refractory disease, particularly in prostate cancer patients with stromal-rich tumors. Collectively, the use of agnostic biomarkers developed for breast cancer stratification has facilitated a precise clinical classification of patients undergoing radical prostatectomy and highlighted the therapeutic potential of targeting estrogen signaling in prostate cancer.

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“…Most miRNA analysis in endometrial cancer is performed using qRT-PCR (96). Recently, TWAS has been proposed for identifying important miRNAs in disease (190). EC was also best predicted when PTEN loss and miR-200a were combined (42).…”

Section: Mirna and Ecmentioning

confidence: 99%

The interplay of sex steroid hormones and microRNAs in endometrial cancer: current understanding and future directions

Thakur

Thakur²

2023

Front. Endocrinol.

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IntroductionEndometrial cancer is a hormone-dependent malignancy, and sex steroid hormones play a crucial role in its pathogenesis. Recent studies have demonstrated that microRNAs (miRNAs) can regulate the expression of sex steroid hormone receptors and modulate hormone signaling pathways. Our aim is to provide an overview of the current understanding of the role of miRNAs in endometrial cancer regulated by sex steroid hormone pathways.MethodsA thorough literature search was carried out in the PubMed database. The articles published from 2018 to the present were included. Keywords related to miRNAs, endometrial cancer, and sex steroid hormones were used in the search.ResultsDysregulation of miRNAs has been linked to abnormal sex steroid hormone signaling and the development of endometrial cancer. Various miRNAs have been identified as modulators of estrogen and progesterone receptor expression, and the miRNA expression profile has been shown to be a predictor of response to hormone therapy. Additionally, specific miRNAs have been implicated in the regulation of genes involved in hormone-related signaling pathways, such as the PI3K/Akt/mTOR and MAPK/ERK pathways.ConclusionThe regulation of sex steroid hormones by miRNAs is a promising area of research in endometrial cancer. Future studies should focus on elucidating the functional roles of specific miRNAs in sex steroid hormone signaling and identifying novel miRNA targets for hormone therapy in endometrial cancer management.

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Integrative Transcriptome-Wide Analyses Uncover Novel Risk-Associated MicroRNAs in Hormone-Dependent Cancers

Cited by 5 publications

References 58 publications

Integrative competing endogenous RNA network analyses identify novel lncRNA and genes implicated in metastatic breast cancer

Integrative competing endogenous RNA network analyses identify novel lncRNA and genes implicated in metastatic breast cancer

Identification of tumor-agnostic biomarkers for predicting prostate cancer progression and biochemical recurrence

The interplay of sex steroid hormones and microRNAs in endometrial cancer: current understanding and future directions

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