Dataset Information

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

ABSTRACT: Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarcinoma of the Mouse Prostate (TRAMP) model and clinically-annotated human tissue samples to identify loss of expression of microRNA-34b as consistently associated with prostate cancer relapse. Mechanistically, this was associated with epigenetics silencing of the MIR34B/C locus and increased DNA copy number loss, selectively in androgen-dependent prostate cancer. In turn, loss of miR-34b resulted in downstream deregulation and overexpression of the "stemness" marker, Sox2. These findings identify loss of miR-34b as a robust biomarker for prostate cancer progression in androgen-sensitive tumors, and anticipate a potential role of progenitor/stem cell signaling in this stage of disease.

SUBMITTER: Forno I

PROVIDER: S-EPMC4479381 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Forno Irene I Ferrero Stefano S Russo Maria Veronica MV Gazzano Giacomo G Giangiobbe Sara S Montanari Emanuele E Del Nero Alberto A Rocco Bernardo B Albo Giancarlo G Languino Lucia R LR Altieri Dario C DC Vaira Valentina V Bosari Silvano S

PloS one 20150624 6

Most men diagnosed with prostate cancer will have an indolent and curable disease, whereas approximately 15% of these patients will rapidly progress to a castrate-resistant and metastatic stage with high morbidity and mortality. Therefore, the identification of molecular signature(s) that detect men at risk of progressing disease remains a pressing and still unmet need for these patients. Here, we used an integrated discovery platform combining prostate cancer cell lines, a Transgenic Adenocarci ...[more]

PMID: 26107383

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Project description:BackgroundLncRNAs act as functional regulators in tumor progression through interacting with various signaling pathways in multiple types of cancer. However, the effect of LINC02418 on colorectal cancer (CRC) progression and the underling mechanisms remain unclear.MethodsLncRNA expression profile in CRC tissues was investigated by the TCGA database. The expressional level of LINC02418 in CRC patients was determined by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Kaplan-Meier analyses was used to investigate the correlation between LINC02418 and overall survival (OS) of CRC patients. Cell proliferative, migratory and invasive abilities were detected by CCK-8 assays, colony formation assays and trans-well assays in HCT116 and LoVo cells which were stably transduced with sh-LINC02418 or sh-NC. The binding between LINC02418 and miR-34b-5p, and the interaction between miR-34b-5p and BCL2 were determined by dual-luciferase assays. Western blot experiments were conducted to further explore the effect of miR-34b-5p on BCL2 signaling pathway. Rescue experiments were performed to uncover the role of LINC02418/miR-34b-5p/BCL2 axis in CRC progression.ResultsLINC02418 was upregulated in human colon cancer samples when compared with adjacent tissue, and its high expressional level correlated with poor prognosis of CRC patients. LINC02418 promoted cancer progression by enhancing tumor growth, cell mobility and invasiveness of colon cancer cells. Additionally, LINC02418 could physically bind to miR-34b-5p and subsequently affect BCL2 signaling pathway. Down-regulation of LINC02418 reduced cell proliferation, while transfection of miR-34b-5p inhibitor or BCL2 into LINC02418-silenced CRC cells significantly promoted CRC cells growth.ConclusionsLINC02418 was upregulated in human CRC samples and could be used as the indicator for prediction of prognosis. LINC02418 acted as a tumor driver by negatively regulating cell apoptosis through LINC02418/miR-34b-5p/BCL2 axis in CRC.

Dataset Information

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

Publications

Deregulation of MiR-34b/Sox2 Predicts Prostate Cancer Progression.

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