Circulating Long Noncoding RNA as a Potential Target for Prostate Cancer.
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ABSTRACT:
SUBMITTER: Su YJ
PROVIDER: S-EPMC4490497 | biostudies-literature | 2015
REPOSITORIES: biostudies-literature
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Project description:High-throughput techniques have identified numerous antisense (AS) transcripts and long non-coding RNAs (ncRNAs). However, their significance in cancer biology remains largely unknown. Here, we report an androgen-responsive long ncRNA, CTBP1-AS, located in the AS region of C-terminal binding protein 1 (CTBP1), which is a corepressor for androgen receptor. CTBP1-AS is predominantly localized in the nucleus and its expression is generally upregulated in prostate cancer. CTBP1-AS promotes both hormone-dependent and castration-resistant tumour growth. Mechanistically, CTBP1-AS directly represses CTBP1 expression by recruiting the RNA-binding transcriptional repressor PSF together with histone deacetylases. CTBP1-AS also exhibits global androgen-dependent functions by inhibiting tumour-suppressor genes via the PSF-dependent mechanism thus promoting cell cycle progression. Our findings provide new insights into the functions of ncRNAs that directly contribute to prostate cancer progression.
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Project description:BackgroundThe incidence of colorectal cancer in humans is high, and it is in the top five for cancer-related morbidity and mortality. It is one of the main threats to human health. The function of long noncoding RNAs in tumor occurrence and development has gradually gained attention in recent years. In increasing numbers of studies, researchers have demonstrated that it plays an important role in the pathogenesis of colorectal cancer.AimTo find out if long noncoding RNA RP5-881L22.5 played a role in the pathogenesis of colorectal cancer in relation to the tumor microenvironment.MethodsWe analyzed the transcriptome data and clinical data in The Cancer Genome Atlas-colon adenocarcinoma. The CIRBERSORT algorithm was applied to evaluate these tumor-infiltrating immune cells in The Cancer Genome Atlas-colon adenocarcinoma cancer tissue samples. Using the "estimate" package in R, we assessed the tumor immune microenvironment. The expression level of RP5-881L22.5 in tumor tissue and adjacent normal tissue samples from 4 pairs of colorectal cancer patients was determined by quantitative reverse transcription PCR. Colorectal cancer cells were tested for invasiveness using a transwell invasion assay after RP5-881L22.5 expression was knocked down.ResultsThe expression of lncRNA RP5-881L22.5 was related to the clinical characteristics of the tumors, and it was negatively related to the infiltration level of immune cells in the tumor microenvironment and the expression of T cell inhibitory receptors. A major function of its coexpressed mRNA was to regulate tumor immunity, such as the immune response. When quantitative reverse transcription PCR was performed on tumor tissues from 4 pairs of colorectal cancer patients, the results showed that RP5-881L22.5 was highly expressed. Subsequently, knocking down the expression of RP5-881L22.5, the invasiveness of colorectal cancer cell lines was reduced, and the apoptosis rate was increased.ConclusionRP5-881L22.5 plays a crucial role in the microenvironment of tumors as well as in the pathogenesis of colorectal cancer. The relationship between RP5-881L22.5 and the tumor immune microenvironment deserves further study.
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2. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in diagnosis of colorectal cancer patients & its relation to tumor staging.
3. Evaluate the clinical utility of detecting long noncoding RNA (CCAT1) expression in precancerous colorectal diseases.
4. Compare long noncoding RNA (CCAT1) expression with traditional marker; carcinoembryonic antigen (CEA) and Carbohydrate antigen 19-9 (CA19-9) in diagnosis of colorectal cancer.
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