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LOC550643, a Long Non-coding RNA, Acts as Novel Oncogene in Regulating Breast Cancer Growth and Metastasis
Kuo-Wang Tsai1, Kian-Hwee Chong2, Chao-Hsu Li2,3
1Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City, Taiwan.
Abstract:
Metastatic disease is responsible for over 90% of death in patients with breast cancer. Therefore, identifying the molecular mechanisms that regulate metastasis and developing useful therapies are crucial tasks. Long non-coding RNAs (lncRNAs), which are non-coding transcripts with >200 nucleotides, have recently been identified as critical molecules for monitoring cancer progression. This study examined the novel lncRNAs involved in the regulation of tumor progression in breast cancer. This study identified 73 metastasis-related lncRNA candidates from comparison of paired isogenic high and low human metastatic breast cancer cell lines, and their expression levels were verified in clinical tumor samples by using The Cancer Genome Atlas. Among the cell lines, a novel lncRNA, LOC550643, was highly expressed in breast cancer cells. Furthermore, the high expression of LOC550643 was significantly correlated with the poor prognosis of breast cancer patients, especially those with triple-negative breast cancer. Knockdown of LOC550643 inhibited cell proliferation of breast cancer cells by blocking cell cycle progression at S phase. LOC550643 promoted important in vitro metastatic traits such as cell migration and invasion. Furthermore, LOC550643 could inhibit miR-125b-2-3p expression to promote breast cancer cell growth and invasiveness. In addition, by using a xenograft mouse model, we demonstrated that depletion of LOC550643 suppressed the lung metastatic potential of breast cancer cells. Overall, our study shows that LOC550643 plays an important role in breast cancer cell metastasis and growth, and LOC550643 could be a potential diagnosis biomarker and therapeutic target for breast cancer.
Insights
This study identifies LOC550643 as a novel long non-coding RNA (lncRNA) driving breast cancer metastasis and growth. Its high expression correlates with poor prognosis, suggesting it as a potential therapeutic target and diagnostic biomarker for breast cancer.
Area of Science:
- Molecular Oncology
- Cancer Genomics
- RNA Biology
Background:
- Metastatic breast cancer causes most patient deaths, necessitating research into metastasis regulation.
- Long non-coding RNAs (lncRNAs) are emerging as key regulators of cancer progression.
- Identifying novel lncRNAs in breast cancer metastasis is crucial for developing new therapies.
Purpose of the Study:
- To identify and characterize novel long non-coding RNAs (lncRNAs) involved in breast cancer metastasis.
- To investigate the role of a specific novel lncRNA, LOC550643, in breast cancer progression and patient prognosis.
Main Methods:
- Comparative analysis of lncRNA expression in high and low metastatic breast cancer cell lines.
- Validation of lncRNA expression in clinical tumor samples using The Cancer Genome Atlas (TCGA).
- Functional studies including gene knockdown, cell proliferation assays, migration and invasion assays, and xenograft mouse models.
Main Results:
- Identified 73 metastasis-related lncRNA candidates, including the novel lncRNA LOC550643, which was highly expressed in breast cancer.
- High LOC550643 expression correlated significantly with poor patient prognosis, particularly in triple-negative breast cancer.
- Knockdown of LOC550643 inhibited cell proliferation, migration, invasion, and lung metastasis in vivo, partly by inhibiting miR-125b-2-3p.
Conclusions:
- LOC550643 plays a critical role in promoting breast cancer cell growth and metastasis.
- LOC550643 represents a potential diagnostic biomarker and therapeutic target for breast cancer, especially aggressive subtypes.
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