miR-301a expression: A prognostic marker for prostate cancer

Damodaran, Chendil; Das, Trinath P.; John, Axel; Suman, Suman; Kolluru, Venkatesh; Morris, Targhee J.; E, Faber; Shesh, N.; Messer, Jamie; Alatassi, Houda; Ankem, Murali K.

doi:10.1016/j.urolonc.2016.03.009

Cited by 23 publications

(17 citation statements)

References 32 publications

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“…Specifically, the ratio of epithelial markers (e.g., E-cadherin) and mesenchymal markers (e.g., β-catenin, snail, slug, and vimentin) may determine adhesion, polarity, and invasive characteristics of cancer cells, dictating tumor metastasis [ 51 , 52 ]. We and others have reported the role of EMT in prostate cancer metastasis [ 53 – 55 ]. WA has been shown to downregulate EMT markers such as Vimentin and β-catenin in breast cancer stem cells [ 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Oral administration of withaferin A inhibits carcinogenesis of prostate in TRAMP model

et al. 2016

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We previously reported that withaferin A (WA), a natural compound, deters prostate cancer by inhibiting AKT while inducing apoptosis. In the current study, we examined its chemopreventive efficacy against carcinogenesis in the prostate using the transgenic adenocarcinoma of mouse prostate (TRAMP) model. Two distinct sets of experiments were conducted. To determine whether WA delays tumor progression, it was given before cancer onset, at week 6, and until week 44. To determine its effect after the onset of prostate cancer, it was given from weeks 12 to 35. In both strategies, oral administration of WA effectively suppressed tumor burden when compared to vehicle-treated animals. No toxicity was seen in treated animals at gross pathological examination. Western blot analysis and immunohistochemistry of tumor sections revealed that in TRAMP controls, AKT and pAKT were highly expressed while nuclear FOXO3a and Par-4 were downregulated. On the contrary, treated mice showed inhibition of AKT signaling and activation of FOX03a-Par-4-induced cell death. They also displayed inhibition of mesenchymal markers such as β-catenin, vimentin, and snail as well as upregulation of E-cadherin. Because expressions of the angiogenic markers factor VIII and retic were downregulated, an anti-angiogenic role of WA is suggested. Overall, our results suggest that WA could be a promising anti-cancer agent that effectively inhibits carcinogenesis of the prostate.

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Section: Discussionmentioning

confidence: 99%

Oral administration of withaferin A inhibits carcinogenesis of prostate in TRAMP model

et al. 2016

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“…Firstly the differentially expressed (DE) or dysregulated microRNAs from large-scale microRNA expression data were extracted as outliers and then the candidates were further validated by low-throughput experiments, such as real-time PCR, etc. [ 3 , 10 , 11 ]. Although experimental methods are powerful enough to detect the abnormal change of microRNA expression between different condition groups, e.g., primary PCa (PPCa) and metastatic PCa (MPCa) [ 12 ], it is not easy to identify the driver or key molecules at the systems level.…”

Section: Introductionmentioning

confidence: 99%

Biomarker microRNAs for prostate cancer metastasis: screened with a network vulnerability analysis model

et al. 2018

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BackgroundProstate cancer (PCa) is a fatal malignant tumor among males in the world and the metastasis is a leading cause for PCa death. Biomarkers are therefore urgently needed to detect PCa metastatic signature at the early time. MicroRNAs are small non-coding RNAs with the potential to be biomarkers for disease prediction. In addition, computer-aided biomarker discovery is now becoming an attractive paradigm for precision diagnosis and prognosis of complex diseases.MethodsIn this study, we identified key microRNAs as biomarkers for predicting PCa metastasis based on network vulnerability analysis. We first extracted microRNAs and mRNAs that were differentially expressed between primary PCa and metastatic PCa (MPCa) samples. Then we constructed the MPCa-specific microRNA-mRNA network and screened microRNA biomarkers by a novel bioinformatics model. The model emphasized the characterization of systems stability changes and the network vulnerability with three measurements, i.e. the structurally single-line regulation, the functional importance of microRNA targets and the percentage of transcription factor genes in microRNA unique targets.ResultsWith this model, we identified five microRNAs as putative biomarkers for PCa metastasis. Among them, miR-101-3p and miR-145-5p have been previously reported as biomarkers for PCa metastasis and the remaining three, i.e. miR-204-5p, miR-198 and miR-152, were screened as novel biomarkers for PCa metastasis. The results were further confirmed by the assessment of their predictive power and biological function analysis.ConclusionsFive microRNAs were identified as candidate biomarkers for predicting PCa metastasis based on our network vulnerability analysis model. The prediction performance, literature exploration and functional enrichment analysis convinced our findings. This novel bioinformatics model could be applied to biomarker discovery for other complex diseases.Electronic supplementary materialThe online version of this article (10.1186/s12967-018-1506-7) contains supplementary material, which is available to authorized users.

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“…Accumulating evidence indicates that miR-301a acts as an oncomiR, and it has been related to tumour progression in several types of cancer. For example, miR-301a has been described as a potential marker for metastasis in prostate cancer, and its high expression was associated with an increased risk of recurrence 16 . Overexpressed miR-301a has also been observed in gastric cancer as well 17 .…”

Section: Introductionmentioning

confidence: 99%

Elevated miR-301a expression indicates a poor prognosis for breast cancer patients

Zheng

Huang

Yao

et al. 2018

Sci Rep

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Although microRNA-301a (miR-301a) has been reported to function as an oncogene in many human cancers, there are limited data regarding miR-301a and breast tumours. In this study, we first detected the expression of miR-301a using an in situ hybridization (ISH) -based classification system in 380 samples of BC tissue, including both non-TNBC (triple-negative breast cancer) and TNBC specimens. Our results suggest that analysing miR-301a expression in breast tissue biopsy specimens at the time of diagnosis could have the potential to identify patients who might be candidates for active surveillance. We validated our results that higher expression of miR-301a is associated with a decreased OS in independent public breast cancer databases, such as TCGA and METABRIC, using the online webtool Kaplan-Meier Plotter, which provided additional powerful evidence to confirm the prognostic value of miR-301a. MiR-301a may serve as a potential therapeutic target for patients with breast cancer. According to our results, miR-301a should be considered, and novel therapeutic options are needed to target this aggressive miR-301a-positive type of breast cancer to reduce recurrence and the mortality rate.

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miR-301a expression: A prognostic marker for prostate cancer

Cited by 23 publications

References 32 publications

Oral administration of withaferin A inhibits carcinogenesis of prostate in TRAMP model

Oral administration of withaferin A inhibits carcinogenesis of prostate in TRAMP model

Biomarker microRNAs for prostate cancer metastasis: screened with a network vulnerability analysis model

Elevated miR-301a expression indicates a poor prognosis for breast cancer patients

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