Identification of hsa-miR-135a target genes in LNCaP and HeLa cell lines
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE45903 | GEO | 2015/03/18
SECONDARY ACCESSION(S): PRJNA196625
REPOSITORIES: GEO
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2015-02-04 | GSE64616 | GEO
Project description:MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs. They act as negative regulators of protein-coding gene expression at the post-transcriptional level via sequence-specific interaction with the 3' UTR of targeted mRNAs. A miR-135a dysregulation has been observed in various cancers, where a dual role of oncomiR or of tumor suppressor has been reported for the cancers profiled to date; however, knowledge is limited to explain these contentious data. In the present study, we investigate the regulation and mechanism of action of miR-135a, including identification of functionally targets that contributes to its actions, in prostate cancer progression. We demonstrate that the expression of miR-135a is regulated by androgens, in a time- and dose-dependent manner and identify miR-135a as a direct target gene of the androgen receptor AR. A functional androgen response element (ARE) is identified in the promoter region of the miR-135a gene and ChIP assay reveal AR protein binding to. Anti-androgen treatment and AR-targeted siRNA knockdown strategy suggest a novel function for miR-135a in AR signaling. In silico prediction, transcriptomic and proteomic combined analyses lead to identify ROCK-1/-2 as two miR-135a-targeted genes. Luciferase reporter assays indicate that these two proteins are miR-135a's direct targets. We finally demonstrate that miR-135a acts through ROCK-1/-2 pathways to affect migration and invasion cellular processes. MiR-135a expression level was lower in surgical cancerous samples compared to paired adjacent non-tumoral tissues and was gradually diminished consistent with cancer progression, suggesting the significance of miR-135a-mediated prostate cancer transformation. Our findings define miR-135a as a candidate tumor suppressor and potential prognostic marker in human prostate cancer.
2015-03-18 | GSE45902 | GEO
Project description:MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs. They act as negative regulators of protein-coding gene expression at the post-transcriptional level via sequence-specific interaction with the 3' UTR of targeted mRNAs. A miR-135a dysregulation has been observed in various cancers, where a dual role of oncomiR or of tumor suppressor has been reported for the cancers profiled to date; however, knowledge is limited to explain these contentious data. In the present study, we investigate the regulation and mechanism of action of miR-135a, including identification of functionally targets that contributes to its actions, in prostate cancer progression. We demonstrate that the expression of miR-135a is regulated by androgens, in a time- and dose-dependent manner and identify miR-135a as a direct target gene of the androgen receptor AR. A functional androgen response element (ARE) is identified in the promoter region of the miR-135a gene and ChIP assay reveal AR protein binding to. Anti-androgen treatment and AR-targeted siRNA knockdown strategy suggest a novel function for miR-135a in AR signaling. In silico prediction, transcriptomic and proteomic combined analyses lead to identify ROCK-1/-2 as two miR-135a-targeted genes. Luciferase reporter assays indicate that these two proteins are miR-135a's direct targets. We finally demonstrate that miR-135a acts through ROCK-1/-2 pathways to affect migration and invasion cellular processes. MiR-135a expression level was lower in surgical cancerous samples compared to paired adjacent non-tumoral tissues and was gradually diminished consistent with cancer progression, suggesting the significance of miR-135a-mediated prostate cancer transformation. Our findings define miR-135a as a candidate tumor suppressor and potential prognostic marker in human prostate cancer.
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Project description:ObjectiveMicroRNAs (miRNAs) are key post-transcriptional regulators of protein translation in humans. They have an essential role in various cancers, including nasopharyngeal carcinoma (NPC). The abnormal expression of miR-21 has been proven to be associated with various types of cancers, including NPC, through its targets. This study provides a systematic view of the roles of miR-21 and its network of targets (hsa-miR-21-3p, hsa-miR-21-5p) that are associated with nasopharyngeal carcinoma.MethodsBioinformatics tools were applied to predict the targets of miR-21. Interactions among the targets of hsa-miR-21-3p/5p were found by the gene MANIA online tool.Results and conclusionIt was found that the target genes are involved in vital biological processes in cancer. In detail, a total of 95 targets of miR-21 were recorded to be associated with NPC. Therefore, they may provide new insights into nasopharyngeal pathogenesis and bring about novel targets for NPC diagnosis as well as therapy in near future.
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