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.
Highlights
Breast cancer is the most common cancer and the second leading cause of cancer deaths among women worldwide (Bray et al, 2018)
We further examined the expression levels of these Long non-coding RNAs (lncRNAs) candidates (514 differentially expressed lncRNAs) in breast cancer cells by using The Cancer Genome Atlas (TCGA) database
Our data revealed that the expression levels of LOC550643 and PVT1 were significantly upregulated in MDA-MB-231-IV2-1 and MDA-MB-231-IV2-2 cells (Figure 2A), whereas the expression levels of LOC652276 were significantly increased in MDA-MB231-IV2-1 cells but not in MDA-MB-231-IV2-2 cells when compared with MDA-MB-231-P cells
Summary
Breast cancer is the most common cancer and the second leading cause of cancer deaths among women worldwide (Bray et al, 2018). Breast cancer is considered a heterogenous disease consisting of at least four molecular subtypes, namely luminal A, luminal B, HER2, and triple negative (or basal-like) subtypes, which are determined on the basis of hormone. LOC550643-miR-125b-2-3p Regulates Breast Cancer Progression receptor status and HER2 expression (Yeo et al, 2014). Long non-coding RNAs (lncRNAs) are an emerging class of ncRNAs with an estimated number of 15,000 human genome transcripts, and these RNAs have been demonstrated to play a crucial role in tumor development (Derrien et al, 2011; Serviss et al, 2014). Abundant evidence indicates that lncRNAs exert their function by interacting with cellular macromolecules such as chromatin, RNAs and proteins to regulate genes important for cell proliferation, motility, invasiveness, and angiogenesis (Serviss et al, 2014; Kumar and Goyal, 2017; Zhang et al, 2020). Despite numerous efforts being made to identify the role of lncRNA in tumor progression, the function of most lncRNAs remains largely unknown
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