The use of long non-coding RNAs as prognostic biomarkers and therapeutic targets in prostate cancer

Arriaga-Canon, Cristian; Rosa-Velázquez, Inti A. De La; González‐Barrios, Rodrigo; Montiel-Manríquez, Rogelio; Oliva-Rico, Diego; Jiménez-Trejo, Francisco; Cortés-González, Carlo César; Herrera, Luis A.

doi:10.18632/oncotarget.25038

Cited by 38 publications

(28 citation statements)

References 139 publications

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“…Though treatable, definitive understanding about the molecular origins of prostate cancer is lacking, and there is considerable controversy about screening methods (1)(2)(3)(4)(5)(6). Continued efforts to identify molecular markers that distinguish between tumors that will remain latent, progress slowly, or progress aggressively are needed (7,8).…”

Section: Introductionmentioning

confidence: 99%

BRG1 is a prognostic indicator and a potential therapeutic target for prostate cancer

Muthuswami

Bailey

Radhakrishnan

et al. 2018

Preprint

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BRG1 is one of two mutually exclusive ATPases that function as the catalytic subunit of human SWI/SNF chromatin remodeling enzymes. BRG1 has been identified as a tumor suppressor in some cancer types but has been shown to be expressed at elevated levels, relative to normal tissue, in other cancers. Using the TCGA (The Cancer Genome Atlas) prostate cancer database, we determined that BRG1 mRNA and protein expression is elevated in prostate tumors relative to normal prostate tissue. Only 3 of 491 (0.6%) sequenced tumors showed amplification of the locus or mutation in the protein coding sequence, arguing against the idea that elevated expression due to amplification or expression of a mutant BRG1 protein is associated with prostate cancer. Kaplan-Meier survival curves showed that BRG1 expression in prostate tumors inversely correlated with survival. However, BRG1 expression did not correlate with Gleason score/ISUP Grade Group, indicating it is an independent predictor of tumor progression/patient outcome. To experimentally assess BRG1 as a possible therapeutic target, we treated prostate cancer cells with a biologic inhibitor called ADAADi that targets the activity of the SNF2 family of ATPases in biochemical assays but showed specificity for BRG1 in prior tissue culture experiments. The inhibitor decreased prostate cancer cell proliferation and induced apoptosis.When directly injected into xenografts established by injection of prostate cancer cells in mouse flanks, the inhibitor decreased tumor growth and increased survival. These results indicate the efficacy of pursuing BRG1 as both an indicator of patient outcome and as a therapeutic target.

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Section: Introductionmentioning

confidence: 99%

BRG1 is a prognostic indicator and a potential therapeutic target for prostate cancer

Muthuswami

Bailey

Radhakrishnan

et al. 2018

Preprint

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“…Long non–coding RNAs are largely recognized as important players in cancer disease [ 7 , 51 ], including haematological malignancies [ 16 , 52 , 53 ]. In addition, considering that lncRNA expression is tightly controlled and exhibits even higher cell specificity than proteins, lncRNAs are emerging as a promising class of biomarkers and/or potential therapeutic targets [ 54 , 55 , 56 , 57 ]. Indeed, several lncRNA signatures for different tumours such as large–B–cell lymphoma, ovarian cancer, breast cancer and other oncological diseases have been reported [ 12 , 13 , 14 , 37 , 58 , 59 , 60 , 61 , 62 ].…”

Section: Discussionmentioning

confidence: 99%

lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study

Affinito

Pane

Smaldone

et al. 2020

Cancers

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Long non–coding RNAs (lncRNAs) are emerging as key gene regulators in the pathogenesis and development of various cancers including B lymphoblastic leukaemia (B–ALL). In this pilot study, we used RNA–Seq transcriptomic data for identifying novel lncRNA–mRNA cooperative pairs involved in childhood B–ALL pathogenesis. We conceived a bioinformatic pipeline based on unsupervised PCA feature extraction approach and stringent statistical criteria to extract potential childhood B–ALL lncRNA signatures. We then constructed a co–expression network of the aberrantly expressed lncRNAs (30) and protein–coding genes (754). We cross–validated our in–silico findings on an independent dataset and assessed the expression levels of the most differentially expressed lncRNAs and their co–expressed mRNAs through ex vivo experiments. Using the guilt–by–association approach, we predicted lncRNA functions based on their perfectly co–expressed mRNAs (Spearman’s correlation) that resulted closely disease–associated. We shed light on 24 key lncRNAs and their co–expressed mRNAs which may play an important role in B–ALL pathogenesis. Our results may be of clinical utility for diagnostic and/or prognostic purposes in paediatric B–ALL management.

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“…[12][13][14][15] Studies used lncRNA microarrays or RNA-sequencing to discover promising lncRNAs in ESCC. In addition, researchers have revealed that lncRNAs can be used as potential diagnostic biomarkers for esophageal squamous cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

“…Even, lncRNAs could predict the prognosis of many malignancies. [12][13][14][15] Studies used lncRNA microarrays or RNA-sequencing to discover promising lncRNAs in ESCC. 16,17 However, these studies revealed different lncRNAs.…”

Section: Discussionmentioning

confidence: 99%

Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma

Xiao

Chang

et al. 2019

J of Cellular Biochemistry

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Esophageal cancer is one of the most lethal malignancies worldwide, and esophageal squamous cell carcinoma (ESCC) is the dominant histological type. However, the long noncoding RNA (lncRNA) alterations in ESCC have not been elucidated to date. In this study, reliable databases from Gene Expression Omnibus (GEO), which analyzed lncRNA expression in ESCC tumor tissues and adjacent normal tissues were searched, and common differentially expressed lncRNAs and genes were analyzed. Next, cis‐ trans analysis was performed to predict the underlying relationships between altered lncRNAs and mRNAs, and the lncRNA‐mRNA regulatory network was established. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses of altered lncRNA‐related genes were performed. The promising lncRNA HCG22 was validated by quantitative polymerase chain reaction (qPCR), and clinicopathological data were collected to identify the relationship between lncRNA HCG22 expression level and clinical features. Finally, Transwell assays were performed to explore the biological functions of lncRNA HCG22 in ESCC cells. Two hundred forty‐one lncRNAs and 835 mRNAs were observed to be remarkably altered between ESCC tumor tissues and adjacent normal tissues. The lncRNA‐mRNA regulatory network showed the coexpression association between lncRNA HCG22 and SPINK7 and ADAMTS12. GO and KEGG analyses showed that HCG22 and ADAMTS12 had potential biological functions in the cell migration of ESCC. The downregulation of lncRNA HCG22 in ESCC tumor tissues was validated by qPCR, and the clinicopathological data showed a noticeable correlation between lncRNA HCG22 expression level and the ESCC differentiational degree and clinical TNM stage. Kaplan‐Meier analysis showed that patients with ESCC having low lncRNA HCG22 expression in ESCC tissues had considerably shorter overall survival compared with patients with ESCC having high lncRNA HCG22 expression. Following Transwell assays confirmed the migratory role of lncRNA HCG22 in ESCC cells. In conclusion, lncRNA HCG22 was downregulated in ESCC tissues and can be a migration inhibitor of ESCC cells, and SPINK7 and ADAMTS12 are promising to be the regulatory targets of lncRNA HCG22.

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The use of long non-coding RNAs as prognostic biomarkers and therapeutic targets in prostate cancer

Cited by 38 publications

References 139 publications

BRG1 is a prognostic indicator and a potential therapeutic target for prostate cancer

BRG1 is a prognostic indicator and a potential therapeutic target for prostate cancer

lncRNAs–mRNAs Co–Expression Network Underlying Childhood B–Cell Acute Lymphoblastic Leukaemia: A Pilot Study

Comprehensive bioinformatics analysis identifies lncRNA HCG22 as a migration inhibitor in esophageal squamous cell carcinoma

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