Dataset Information

Roles of DANCR/microRNA-518a-3p/MDMA ceRNA network in the growth and malignant behaviors of colon cancer cells.

ABSTRACT:

Background

The competing endogenous RNA (ceRNA) networks of long non-coding RNAs (lncRNAs) and microRNAs (miRs) have aroused wide concerns. The study aims to investigate the roles of lncRNA DANCR-associated ceRNA network in the growth and behaviors of colon cancer (CC) cells.

Methods

Differentially expressed lncRNAs between CC and paracancerous tissues were analyzed using microarrays and RT-qPCR. Follow-up studies were conducted to evaluate the correlation between DANCR expression and prognosis of CC patients. Loss-of-functions of DANCR were performed to identify its role in the malignant behaviors of CC cells. Sub-cellular localization of DANCR and the potential targets of DANCR were predicted and validated. Cells with inhibited DANCR were implanted into nude mice to evaluate the tumor formation and metastasis in vivo.

Results

DANCR was highly-expressed in CC tissues and cell lines, and higher levels of DANCR were linked with worse prognosis and less survival time of CC patients. Silencing of DANCR inhibited proliferation, viability, metastasis and resistance to death of CC cells. DANCR was found to be sub-localized in cytoplasmic matrix and to mediate murine double minute 2 (MDM2) expression through sponging miR-518a-3p in CC cells, during which the Smad2/3 signaling was activated. Likewise, silencing of DANCR in CC cells inhibited tumor formation and metastasis in vivo.

Conclusion

This study provided evidence that silencing of DANCR might inhibit the growth and metastasis of CC cells through the DANCR/miR-518a-3p/MDM2 ceRNA network and the defect of Smad2/3 while activation of the p53 signaling pathways. This study may offer novel insights in CC treatment.

SUBMITTER: Sun Y

PROVIDER: S-EPMC7236548 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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Publications

Roles of DANCR/microRNA-518a-3p/MDMA ceRNA network in the growth and malignant behaviors of colon cancer cells.

Sun Yi Y Cao Bin B Zhou Jingzhen J

BMC cancer 20200518 1

<h4>Background</h4>The competing endogenous RNA (ceRNA) networks of long non-coding RNAs (lncRNAs) and microRNAs (miRs) have aroused wide concerns. The study aims to investigate the roles of lncRNA DANCR-associated ceRNA network in the growth and behaviors of colon cancer (CC) cells.<h4>Methods</h4>Differentially expressed lncRNAs between CC and paracancerous tissues were analyzed using microarrays and RT-qPCR. Follow-up studies were conducted to evaluate the correlation between DANCR expression ...[more]

PMID: 32423468

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Project description:Two mature miRNA species may be generated from the 5' and 3' arms of a pre-miRNA precursor. In most cases, only one species remains while the complementary species is degraded. However, co-existence of miRNA-5p and -3p species is increasingly being reported. In this work, we aimed to systematically investigate co-expression of miRNA-5p/3p in colon cancer cells in a genome-wide analysis, and to examine cross-targeting of the dysregulated miRNAs and 5p/3p species.Four colon cancer cell lines were examined relative to two normal colon tissues. Of the 1,190 miRNAs analyzed, 92 and 36 were found to be up- or down-regulated, respectively, in cancer cells. Nineteen co-expressed miRNA-5p/3p pairs were further identified suggesting frequent 5p/3p co-accumulation in colon cancer cells. Of these, 14 pairs were co-up-regulated and 3 pairs were co-down-regulated indicating concerted 5p/3p dysregulation. Nine dysregulated miRNA pairs fell into three miRNA gene families, namely let-7, mir-8/200 and mir-17, which showed frequent cross-targeting in the metastasis process. Focusing on the let-7d-5p/3p pair, the respectively targeted IGF1R and KRAS were shown to be in a reverse relationship with expression of the respective miRNA, which was confirmed in transient transfection assays using let-7d mimic or inhibitor. Targeting of KRAS by let-7d was previous reported; targeting of IGF1R by let-7d-5p was confirmed in luciferase assays in this study. The findings of let-7d-5p/3p and multiple other miRNAs targeting IGF1R, KRAS and other metastasis-related factors suggest that 5p/3p miRNAs contribute to cross-targeting of multiple cancer-associated factors and processes possibly to evade functional abolishment when any one of the crucial factors are inactivated.miRNA-5p/3p species are frequently co-expressed and are coordinately regulated in colon cancer cells. In cancer cells, multiple cross-targeting by the miRNAs, including the co-existing 5p/3p species, frequently occurs in an apparent safe-proof scheme of miRNA regulation of important tumorigenesis processes. Further systematic analysis of co-existing miRNA-5p/3p pairs in clinical tissues is important in elucidating 5p/3p contributions to cancer pathogenesis.

Dataset Information

Roles of DANCR/microRNA-518a-3p/MDMA ceRNA network in the growth and malignant behaviors of colon cancer cells.

Background

Methods

Results

Conclusion

Publications

Roles of DANCR/microRNA-518a-3p/MDMA ceRNA network in the growth and malignant behaviors of colon cancer cells.

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