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Author Spotlight: A Computational Pipeline for Analyzing Chimeric Noncoding RNA-Target RNA Interactions in High-Throughput Sequencing Data
Published on: December 1, 2023
Long noncoding RNA DANCR aggravates retinoblastoma through miR-34c and miR-613 by targeting MMP-9
Jing-Xian Wang1, Yuan Yang2, Kun Li3
1Department of General Surgery Five, Cangzhou Central Hospital, Cangzhou, Hebei, China.
Abstract:
Long non-coding RNAs (lncRNAs) have been identified to play vital roles in cancers, including human retinoblastoma (RB). However, the deepgoing mechanism is still ambiguous. In present study, we investigate the biological role of lncRNA DANCR (differentiation antagonizing non-protein coding RNA) in carcinogenesis of RB. Results revealed that DANCR was up-regulated in RB tissue and cell lines. Moreover, the ectopic overexpression of DANCR indicated poor overall survivals and disease free survival (DFS) for RB patients. In vitro and in vivo experiments, DANCR knockdown suppress the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) correlated protein (N-cadherin, Vimentin) of RB cells. Bioinformatics analysis predicted that miR-34c and miR-613 targeted with 3'-UTR of DANCR, besides, miR-34c and miR-613 also targeted with 3'-UTR of MMP-9, which was validated by luciferase reporter assay. Functional experiments demonstrated that miR-34c and miR-613 could reverse the oncogenic function of DANCR in RB tumorigenesis. In conclusion, our results reveal that DANCR function as competing endogenous RNA (ceRNA) for miR-34c and miR-613 to modulate progression and metastasis in RB oncogenesis via targeting MMP-9, presenting the in-depth regulation of DANCR in RB and providing a novel insight for ceRNA mechanism for RB.
Insights
Long non-coding RNA DANCR promotes retinoblastoma (RB) progression by acting as a competing endogenous RNA for miR-34c and miR-613, impacting metastasis via MMP-9.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Long non-coding RNAs (lncRNAs) are implicated in cancer development, but their specific roles in retinoblastoma (RB) remain unclear.
- Understanding the molecular mechanisms of lncRNAs in RB is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the biological role of the lncRNA DANCR (differentiation antagonizing non-protein coding RNA) in the carcinogenesis of human retinoblastoma.
- To elucidate the mechanism by which DANCR influences RB progression and metastasis.
Main Methods:
- Quantitative real-time PCR to assess DANCR expression in RB tissues and cell lines.
- In vitro (cell proliferation, migration, invasion assays) and in vivo (tumor xenograft) experiments to evaluate DANCR's functional impact.
- Bioinformatics analysis and luciferase reporter assays to identify and validate interactions between DANCR, microRNAs (miR-34c, miR-613), and MMP-9.
Main Results:
- DANCR was significantly upregulated in RB tissues and cell lines, correlating with poor patient survival.
- Knockdown of DANCR suppressed RB cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT).
- DANCR acted as a competing endogenous RNA (ceRNA) for miR-34c and miR-613, modulating MMP-9 expression and thereby influencing RB progression and metastasis.
Conclusions:
- DANCR plays a critical oncogenic role in retinoblastoma progression and metastasis.
- The DANCR/miR-34c/miR-613/MMP-9 axis represents a novel ceRNA mechanism in RB tumorigenesis.
- Targeting DANCR may offer a potential therapeutic strategy for retinoblastoma.
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