Dataset Information

Species-specific function of microRNA-7702 in human colorectal cancer cells via targeting TADA1.

ABSTRACT: Colorectal cancer (CRC) is highly invasive, and an increasing number of studies report that microRNAs (miRNAs) are involved in CRC cell invasion and metastasis. However, these studies focus on miRNAs with clear functional targets, often overlooking obscure miRNAs. Using TCGA data analysis, we compared differentially expressed miRNAs in colon and rectal adenocarcinoma (stages N0 and N1/N2) to identify miRNAs involved in invasion and metastasis; one identified candidate miRNA was miR-7702. Bioinformatics analysis identified TADA1 as a possible target gene of miR-7702. The relationship between TADA1 and miR-7702 was analyzed using the Oncomine database, CRC tissues at different stages, and CRC cell lines with different metastatic properties. We used a dual luciferase-reporter assay to verify the interaction between miR-7702 and TADA1. We altered miR-7702 and TADA1 expression levels using transfection, and measured cell migration and invasion abilities. The results revealed a negative correlation between miR-7702 and TADA1 in CRC. miR-7702 was significantly downregulated in human CRC cell lines with high invasion capacity. Its overexpression suppressed human CRC cell migration and invasion by directly inhibiting TADA1. This regulatory effect of miR-7702 on TADA1 was observed in human CRC cells but not in mouse cells. These findings indicate that miR-7702 acts as a tumor suppressor in CRC by inhibiting cell migration and invasion, possibly through direct TADA1 inhibition. Our results demonstrate for the first time that miR-7702 and TADA1 are biologically functional in human CRC cells and reveal that the presence and function of miR-7702 may be species-specific.

SUBMITTER: Liu H

PROVIDER: S-EPMC6129515 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Species-specific function of microRNA-7702 in human colorectal cancer cells via targeting TADA1.

Liu Han H Li Dongdong D Fang Hua H Ning Junnan J

American journal of translational research 20180815 8

Colorectal cancer (CRC) is highly invasive, and an increasing number of studies report that microRNAs (miRNAs) are involved in CRC cell invasion and metastasis. However, these studies focus on miRNAs with clear functional targets, often overlooking obscure miRNAs. Using TCGA data analysis, we compared differentially expressed miRNAs in colon and rectal adenocarcinoma (stages N0 and N1/N2) to identify miRNAs involved in invasion and metastasis; one identified candidate miRNA was miR-7702. Bioinfo ...[more]

PMID: 30210694

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Project description:Distant metastasis is the major cause of mortality in colorectal cancer (CRC). We performed a systemic, comprehensive discovery for expression patterns of metastasis-specific microRNAs (miRNAs) by directly comparing primary CRCs (pCRCs) and matched liver metastases (LMs) and evaluated the feasibility of their clinical application as metastasis-specific biomarkers.CRC metastasis-specific miRNA profiles were generated by analyzing nine pairs of pCRC and LM tissues, followed by quantitative validation in an independent cohort of 58 pairs of matched pCRC and LM tissues. We evaluated associations between miRNA expression and patient survival and ability to predict metastasis in another 84 patients with CRC. Subsequently, associations were quantitatively validated in 175 CRC tissues and 169 serum samples. Kaplan-Meier, Cox regression, and logistic regression analyses were used. All statistical tests were two-sided.Twenty-three miRNAs were identified that were differentially expressed between pCRC and LM (P < .001; FDR < .5). Four miRNAs downregulated in LM (let-7i, miR-10b, miR-221, and miR-320a) and one upregulated miR (miR-885-5p) were quantitatively validated in pCRC (P < .0001). Low let-7i expression in pCRC tissue predicted worsened prognosis (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 1.0 to 24.4, P = .0479) as well as distant metastasis (odds ratio [OR] = 5.5, 95% CI = 1.1 to 26.8, P = .0334). High miR-10b expression in pCRC tissue independently predicted distant metastasis (OR = 4.9, 95% CI = 1.2 to 19.7, P = .0248). High serum miR-885-5p expression independently predicted prognosis (HR = 2.9, 95% CI = 1.1 to 7.5, P = .0323), LN metastasis (OR = 3.0, 95% CI = 1.3 to 7.2, P = .0116), and distant metastasis (OR = 3.1, 95% CI = 1.0 to 10.0, P = .0456), whereas tissue miR-885-5p expression did not. Expression patterns of miRNAs were confirmed by in situ hybridization.We discovered a metastasis-specific miRNA signature in pCRCs and discovered novel tissue- and serum-based CRC metastasis-specific miRNA biomarkers through intensive validation. These unique miRNAs may be clinically applicable to predict prognosis and distant metastasis in CRC.

Dataset Information

Species-specific function of microRNA-7702 in human colorectal cancer cells via targeting TADA1.

Publications

Species-specific function of microRNA-7702 in human colorectal cancer cells via targeting TADA1.

Similar Datasets

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