Abstract
The function and mechanism of long intergenic non-protein coding RNA 974 (LINC00974) are rarely reported in ovarian cancer (OC). The study aimed to investigate how LINC00974 affects the progression of OC. The expression levels of LINC00974, microRNA-33a (miR-33a), and high mobility group box 2 (HMGB2) mRNA were detected by qRT-PCR. The LINC00974/miR-33a/HMGB2 axis was confirmed by dual-luciferase reporter, RNA-binding protein immunoprecipitation (RIP), and biotinylated RNA pull-down assays. A series of in vitro experiments were employed to assess the effects of LINC00974/miR-33a/HMGB2 axis on the proliferation, invasion and epithelial mesenchymal transition (EMT) of OC cells. Results showed that LINC00974 and HMGB2 mRNA expression were upregulated in OC cells, while miR-33a expression was downregulated. HMGB2 was a direct target gene of miR-33a. LINC00974 act as a competing endogenous RNA (ceRNA) to directly bind with miR-33a, thereby upregulated HMGB2 expression. Notably, silencing of LINC00974 suppressed cell proliferation, invasion and EMT of OC cells, whereas miR-33a knockdown partially reversed the phenotypes of LINC00974 on OC cells. Overall, our study demonstrated that LINC00974 sponges miR-33a to promote cell proliferation, invasion, and EMT of OC through HMGB2 upregulation. LINC00974/miR-33a/HMGB2 axis may be an important signaling pathway in the progression of OC.
Highlights
Ovarian cancer (OC) is one of the most common gynecological malignant tumors and the primary cause of cancer death in women globally (La Vecchia, 2017; Webb and Jordan, 2017)
The expression of high mobility group box 2 (HMGB2) messenger RNA (mRNA) was upregulated in SKOV-3, A2780, and OVcAR3 cells compared with the human ovarian surface epithelial cell line (HOSEpiC) cells (Figure 1B, P < 0.01)
Results showed that LINC00974 was mainly located in the cytoplasm of SKOV-3 cells (Figure 1D), indicating that LINC00974 may exert function by sponging miRNA
Summary
Ovarian cancer (OC) is one of the most common gynecological malignant tumors and the primary cause of cancer death in women globally (La Vecchia, 2017; Webb and Jordan, 2017). Incidence of OC in young women is increasing obviously in China (Zhang et al, 2019). In the last few decades, despite great advances have been achieved with scientific researches in the therapy of OC, the 5-year overall survival rate of OC patients is less that 40% by global statistics in 2017 (Siegel et al, 2017). Malignant metastasis and cancer recurrence are the main and severe problems in treatment with OC. There is an urgent need to seek for effective therapeutic targets to improve the prognosis of this cancer
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