Abstract
LncRNA-MIR210HG plays crucial roles in the progression of diverse cancers. However, the expression and function of MIR210HG in ovarian cancer remains unclear. In the present study, we aimed to determine the expression and function of lncRNA-MIR210HG in ovarian cancer under hypoxic conditions. MIR210HG expression in ovarian cancer cells under hypoxic conditions was determined by qPCR analysis, and the distribution was determined by FISH and qPCR analysis based on cell nucleus and cytosol RNA extraction. Epithelial-Mesenchymal Transition (EMT) assay and human umbilical vein endothelial cell-based tube formation and migration assays were employed to determine the potential function of MIR210HG in vitro, followed by establishment of a subcutaneous tumor model in mice. The direct target of MIR210HG was determined by RNA pull-down and western blotting. Furthermore, the expression and clinical correlation of MIR210HG was determined based on malignant tissues from ovarian cancer patients. Our results indicated that MIR210HG was induced by hypoxia, which is HIF-1α dependent and mainly located in the cytosol of ovarian cancer cells. Knockdown of MIR210HG significantly inhibited EMT and tumor angiogenesis in vitro and impaired tumor growth in mice. Molecular investigations indicated that MIR210HG directly targets HIF-1α protein and inhibits VHL-dependent HIF-1α protein degradation in ovarian cancer. Further results demonstrated that MIR210HG was upregulated in ovarian cancer tissues and correlated with tumor progression and poor prognosis of ovarian cancer patients. Our study suggests that hypoxia-induced MIR210HG promotes cancer progression by inhibiting HIF-1α degradation in ovarian cancer, which could be a therapeutic target for ovarian cancer.
Highlights
Ovarian cancer is one of the most challenging diseases in gynecologic oncology, which causes approximately 240,000 new cases and 150,000 deaths every year [1]
To determine the potential role of HIF-1a in hypoxia-induced Long non-coding RNAs (lncRNAs)-MIR210HG expression, siRNA targeting HIF-1a was used to transfect A2780 and SKOV3 cells, and low HIF-1a expression was observed in the cells (Figure 1C). qPCR analysis indicated that knockdown of HIF-1a significantly inhibited lncRNA-MIR210HG expression in A2780 and SKOV3 cells (Figure 1D)
These results indicate that lncRNA-MIR210HG is a hypoxia-induced lncRNA in ovarian cancer, which is mediated by HIF-1a
Summary
Ovarian cancer is one of the most challenging diseases in gynecologic oncology, which causes approximately 240,000 new cases and 150,000 deaths every year [1]. Patients with EOC have a 45.6% 5‐ year survival rate [3,4,5], and despite optimal therapy (surgery and platinum-based chemotherapy), the 5-year survival rate in Stages III and IV is between 18–47% [6, 7]. An effort to understand the underlying mechanism of cancer progression is necessary and beneficial for ovarian cancer therapy. Once a hypoxic and nutrient-poor environment is established, metabolic byproducts and immunosuppressive modulators accumulate [10, 11]. Accumulating evidence indicates that a hypoxic environment causes metastasis, which is attributed to 90% of cancer-related death [14]. Hypoxia is tightly associated with a poor prognosis and high mortality in patients with ovarian cancer [15]. Targeting hypoxia is an effective strategy for cancer therapy
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