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miR-429 inhibits metastasis by targeting KIAA0101 in Soft Tissue Sarcoma
Devyani Samantarrai1, Bibekanand Mallick1
1RNAi and Functional Genomics Laboratory, Department of Life Science, National Institute of Technology Rourkela, Odisha 769008, India.
Abstract:
Soft tissue sarcomas (STS) are a heterogeneous group of rare tumors with high metastatic potential. There being only a handful of publication on metastasis of STS, we investigated the miRNA mediated target gene regulations in modulating the metastatic processes in this cancer. In this study, we amalgamated gene and miRNA expression profiles of high-grade STS samples with miRNA target predictions and identified miR-429 targeting KIAA0101 as a novel pair, which remain unexplored in STS metastasis. We validated their expression in metastatic fibrosarcoma cell line, HT1080 and performed several functional assays using miRNA mimics and KIAA0101 over-expression vector to confirm their role in metastasis. We observed miR-429 is downregulated in HT1080 cells and acting as an anti-metastatic miRNA that inhibited proliferation, migration, anchorage independent growth and invasion by de-repressing KIAA0101. Moreover, the renilla luciferase reporter assay confirmed that miR-429 targets KIAA0101 by binding to its 3/UTR and influence its expression. Taken together, our work demonstrated miR-429 mediates deregulation of KIAA0101 by acting as an anti-metastatic miRNA that targets KIAA0101 pro-metastatic gene during metastasis of STS.
Insights
This study identifies microRNA-429 (miR-429) as a novel anti-metastatic factor in soft tissue sarcomas (STS). It inhibits cancer spread by targeting the KIAA0101 gene, offering new insights into STS metastasis.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Soft tissue sarcomas (STS) are rare, heterogeneous cancers with significant metastatic potential.
- Limited research exists on the mechanisms driving STS metastasis.
- MicroRNAs (miRNAs) are key regulators of gene expression implicated in various cancers.
Purpose of the Study:
- To investigate miRNA-mediated target gene regulation in soft tissue sarcoma (STS) metastasis.
- To identify novel miRNA-gene interactions involved in the metastatic process of STS.
- To explore the role of miR-429 and its target KIAA0101 in STS metastasis.
Main Methods:
- Amalgamation of gene and miRNA expression profiles from high-grade STS samples.
- Utilized miRNA target prediction algorithms to identify potential interactions.
- Validated miRNA and gene expression in the HT1080 fibrosarcoma cell line.
- Performed functional assays using miRNA mimics and KIAA0101 overexpression vectors.
- Conducted a luciferase reporter assay to confirm direct targeting.
Main Results:
- Identified a novel interaction between miR-429 and KIAA0101 in STS metastasis.
- miR-429 was found to be downregulated in metastatic fibrosarcoma cells (HT1080).
- Overexpression of miR-429 inhibited proliferation, migration, anchorage-independent growth, and invasion.
- miR-429 directly targets KIAA0101 at its 3'UTR, leading to its downregulation.
- KIAA0101 acts as a pro-metastatic gene targeted by the anti-metastatic miR-429.
Conclusions:
- miR-429 functions as an anti-metastatic miRNA in soft tissue sarcomas.
- The miR-429/KIAA0101 axis plays a critical role in regulating STS metastasis.
- This finding provides a potential therapeutic target for inhibiting STS metastasis.
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