Background/Aims: Long noncoding RNAs (lncRNAs) play a critical role in tumorigenesis and progression of ovarian cancer (OC). This study focused on the function and potential mechanism toward LEMD1-AS1 (LEMD1 antisense RNA 1) in the progression of ovarian cancer. Materials and Methods: The expression of LEMD1-AS1 in OC tissues was evaluated in TCGA and Gene Expression Omnibus datasets (GSE119056) and confirmed in OC cell lines via qRT-PCR (quantitative real-time polymerase chain reaction). Then, the location of LEMD1-AS1 in the cytoplasmic and nuclear RNAs extracted from OV cells was detected by qRT-PCR. Cell Counting Kit-8 (CCK-8), colony formation, wound-healing and transwell assays were applied to examine cell viability, proliferation, migration and invasion, respectively. Further, the effect of LEMD1-AS1 on OC tumor growth was determined via subcutaneous xenotransplanted tumor model. The potential target for LEMD1-AS1 was validated via dual-luciferase activity assay, RNA pull-down and RNA immunoprecipitation. Results: The expression of LEMD1-AS1 was decreased in OC tissues and cell lines. Forced overexpression of LEMD1-AS1 inhibited the proliferation, migration and invasion of ovarian cancer cells and transplanted tumor growth in nude mice. We found that LEMD1-AS1 was mainly located in the cytoplasm of OC cells and contained complementary sites of miR-183-5p. Mechanistically, our results showed that LEMD1-AS1 could directly interact with miR-183-5p and tumor protein p53 (TP53). The anti-tumor role of LEMD1-AS1 on OC progression depended on miR-183-5p-mediated TP53 expression. Conclusion: LEMD1-AS1 suppresses OC progression through sponging miR-183-5p and regulation of TP53, suggesting a novel biomarker and target for OC.
Ovarian cancer is the leading cause of death in gynecologic malignancies. Ovarian cancer as a metastatic malignant tumor is highly recurrent and prone to drug resistance. Bioactive peptides are an emerging area of biomedical research in reducing resistance of tumor cell to drugs. In this paper, we investigated the effects and mechanisms of bioactive hexapeptide (PGPIPN) derived in milk protein on the sensitivity of ovarian cancer cells to cis-dichlorodiammine platinum (DDP). Human ovarian cancer cell lines (SKOV3 and COC1), their DDP-resistant sublines (SKOV3/DDP and COC1/DDP) and human primary ovarian cancer cells were cultured in vitro under the combined treatment of DDP (close to IC50) and different concentrations of PGPIPN. The viabilities, apoptosis and cell cycle changes were respectively measured by WST-8 and flow cytometry. The mRNA and protein expression levels of HSF1, HSP70, MDR1, ERCC1 and β-actin gene were respectively assayed by RT-qPCR and western blotting. The results showed that PGPIPN significantly increased the sensitivity of human ovarian cancer cells to DDP in inhibiting viability and inducing apoptosis in vitro. But the effects in sensitive cells were lower than DDP-resistant cells. PGPIPN significantly changed the cell cycles in all human ovarian cancer cells, which leaded to a significant increase in the percentage of cells blocked at G2/M phase and decrease the percentage of cells at G1 phases in a dose-dependent manner. PGPIPN affected the expression levels of HSF1, HSP70, MDR1 and ERCC1 genes. Compared with cells in DDP treatment alone, the expression levels of HSF1 and HSP70 in human ovarian cancer cells treated with DDP and PGPIPN together significantly decreased in dose-dependent manner. PGPIPN significantly decreased MDR1 and ERCC1 of drug-resistant ovarian cancer cell lines and human primary ovarian cancer cell in a dose-dependent manner. Pifithrin-μ (PFTμ, HSP70 inhibitor) decreased or removed the effects of peptide in increasing the sensitivity of ovarian cancer cells to DDP. This suggests that PGPIPN enhanced the sensitivity of ovarian cancer cells to DDP partially via reducing the activity of HSF1/HSP70 signaling pathway, thus inducing cell apoptosis and decreasing repairment of DNA damage.
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