Background: Ovarian cancer (OC) is a common fatal malignant tumor of female reproductive system worldwide. Growing studies have proofed that circular RNAs (circRNAs) engage in the regulation of various types of cancers. However, the underlying biological functions and effect mechanism of circular RNA_LARP4 (circ_LARP4) in OC have not been explored. Methods: Quantitative real-time polymerase chain reaction (qRT-PCR) analysis was used to detect the expression of circ_LARP4 in OC cells. The function of circ_LARP4 was measured by cell counting kit-8 (CCK-8), colony formation assay and transwell assay. RNA immunoprecipitation (RIP) assay and luciferase reporter assays assessed the binding correlation between miR-513b-5p and circ_LARP4 (or LARP4). Results: The expression of circ_LARP4 in OC cells was much lower than that in human normal ovarian epithelial cells. Overexpressing circ_LARP4 impaired cell proliferation, invasion and migration abilities. Circ_LARP4 worked as a competing endogenous RNA (ceRNA) to sponge miR-513b-5p. Furthermore, LARP4 was indirectly modulated by circ_LARP4 as the downstream target of miR-513b-5p, as well as the host gene of circ_LARP4. Conclusion: Circ_LARP4 could hamper cell proliferation and migration by sponging miR-513b-5p to regulate the expression of LARP4. This research may provide some referential value to OC treatment.
The standard treatment for node-positive cervical cancer after radical hysterectomy is pelvic radiotherapy and concurrent chemotherapy. Given the potential toxicity of postoperative radiotherapy, we used the lymph node ratio (LNR) to assess the benefit of postoperative radiotherapy in lymph node-positive cervical cancer patients. Data from the Surveillance Epidemiology and End Results database (1988–2010) were analyzed using Kaplan–Meier and Cox regression proportional hazard analysis. A total of 2,269 eligible patients were identified (median follow-up, 78.0 months); 1,863 (82.1%) patients received postoperative radiotherapy. In both univariate and multivariate analysis multivariate analysis, a higher LNR was significantly associated with a poorer outcome. A LNR > 0.16 was associated with poorer cervical cancer-related survival (CCSS) (hazard Ratio [HR] 1.376, confidence interval [CI] 1.082–1.750; P < 0.001) and overall survival (OS) (HR 1.287, CI 1.056–1.569; P = 0.012). Postoperative radiotherapy was only associated with survival benefits in patients with a LNR > 0.16 (CCSS, P < 0.001; OS, P < 0.001) and not in patients with a LNR ≤ 0.16 (CCSS, P = 0.620; OS, P = 0.167); these trends were not affected by number of removed lymph nodes. A higher LNR is associated with a poorer survival in lymph node-positive cervical cancer. The survival benefits of postoperative radiotherapy appear to be limited to patients with a LNR > 0.16.
It has been reported that chemotherapy resistance mainly contributed to treatment failure and poor survival in patients with ovarian cancer. Therefore, clarifying the molecular mechanism and identifying effective strategies to overcome drug resistance may play an important clinical impact on this malignant tumor. In our study, we found that the expression of Glycosyltransferase 8 domain containing 2 (GLT8D2) was significantly upregulated in ovarian cancer samples with CDDP (Cis-dichlorodiammine-platinum) resistance. Biological experiment demonstrate that GLT8D2 overexpression confers CDDP resistance on ovarian cancer cells; however, inhibition of GLT8D2 sensitized ovarian cancer cell lines to CDDP cytotoxicity both in vitro and in vivo. By using affinity purification/mass spectrometry (IP/MS) and reciprocal co-immunoprecipitation (co-IP) analyses, we found that GLT8D2 interacts with fibroblast growth factor receptor 1(FGFR1) in ovarian cancer cells. Furthermore, overexpression of GLT8D2 activated FGFR/PI3K signaling axis and upregulated the phosphorylation levels of FRS2a and AKT (AKT serine/threonine kinase). Importantly, pharmacological inhibition of FGFR and PI3K (phosphatidylinositol 3-kinase) signaling pathway significantly counteracted GLT8D2-induced chemoresistance and enhanced platinum’s therapeutic efficacy in ovarian cancer. Therefore, our findings suggest that GLT8D2 is a potential therapeutic target for the treatment of ovarian cancer; targeting GLT8D2/FGFR/PI3K/AKT signaling axis may represent a promising strategy to enhance platinum response in patients with chemoresistant ovarian cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.