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Long noncoding RNA linc00617 exhibits oncogenic activity in breast cancer
1Department of Breast and Thyroid Surgery, General Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
Abstract:
Protein-coding genes account for only 2% of the human genome, whereas the vast majority of transcripts are noncoding RNAs including long noncoding RNAs. LncRNAs are involved in the regulation of a diverse array of biological processes, including cancer progression. An evolutionarily conserved lncRNA TUNA, was found to be required for pluripotency of mouse embryonic stem cells. In this study, we found the human ortholog of TUNA, linc00617, was upregulated in breast cancer samples. Linc00617 promoted motility and invasion of breast cancer cells and induced epithelial-mesenchymal-transition (EMT), which was accompanied by generation of stem cell properties. Moreover, knockdown of linc00617 repressed lung metastasis in vivo. We demonstrated that linc00617 upregulated the expression of stemness factor Sox2 in breast cancer cells, which was shown to promote the oncogenic activity of breast cancer cells by stimulating epithelial-to-mesenchymal transition and enhancing the tumor-initiating capacity. Thus, our data indicate that linc00617 functions as an important regulator of EMT and promotes breast cancer progression and metastasis via activating the transcription of Sox2. Together, it suggests that linc00617 may be a potential therapeutic target for aggressive breast cancer. © 2015 Wiley Periodicals, Inc.
Insights
Long noncoding RNA (lncRNA) linc00617 promotes breast cancer progression and metastasis by upregulating the stemness factor Sox2. Targeting linc00617 may offer a therapeutic strategy for aggressive breast cancer.
Area of Science:
- Molecular Biology
- Genetics
- Oncology
Background:
- Noncoding RNAs, particularly long noncoding RNAs (lncRNAs), play crucial roles in biological processes, including cancer.
- The lncRNA TUNA is essential for pluripotency in mouse embryonic stem cells.
Purpose of the Study:
- To investigate the role of the human ortholog of TUNA, linc00617, in breast cancer.
- To elucidate the mechanism by which linc00617 influences breast cancer progression and metastasis.
Main Methods:
- Analysis of linc00617 expression in breast cancer samples.
- In vitro studies assessing the effects of linc00617 on cell motility, invasion, and epithelial-mesenchymal-transition (EMT).
- In vivo experiments evaluating the impact of linc00617 knockdown on lung metastasis.
- Investigation of linc00617's effect on Sox2 expression and its downstream consequences.
Main Results:
- Linc00617 was found to be upregulated in breast cancer tissues.
- Overexpression of linc00617 enhanced breast cancer cell motility, invasion, and induced EMT with stem cell properties.
- Knockdown of linc00617 significantly reduced lung metastasis in vivo.
- Linc00617 was shown to upregulate Sox2 expression, promoting EMT and tumor-initiating capacity.
Conclusions:
- Linc00617 is a key regulator of EMT and promotes breast cancer progression and metastasis by activating Sox2 transcription.
- Linc00617 represents a potential therapeutic target for aggressive breast cancer.
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