4.7 Article

LOC550643, a Long Non-coding RNA, Acts as Novel Oncogene in Regulating Breast Cancer Growth and Metastasis

Journal

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fcell.2021.695632

Keywords

breast cancer; ncRNA; metastasis; lncRNA; microRNA

Funding

  1. Ministry of Science and Technology [MOST 106-2320-B-075B-004, MOST 107-2320-B-003-MY2, MOST 109-2320-B-039-062MY2]
  2. Taipei Tzu Chi Hospital
  3. Buddhist Tzu Chi Medical Foundation [TCRD-TPE-109-66, TCRD-TPE-MOST-10817]
  4. China Medical University intramural grant [CMU110Z-06]

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This study identified a novel lncRNA, LOC550643, highly expressed in breast cancer cells, which was significantly correlated with poor prognosis in breast cancer patients. LOC550643 promoted cell migration and invasion, inhibited miR-125b-2-3p expression to promote cancer cell growth and invasiveness. Depletion of LOC550643 suppressed the lung metastatic potential of breast cancer cells, suggesting it could be a potential diagnosis biomarker and therapeutic target for breast cancer.
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.

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