Ran Li

LINC00665 affects the malignant biological behavior of ovarian cancer via the miR-148b-3p/KLF5

This study investigated the expression and clinical significance of long intergenic noncoding RNA 00665 (LINC00665) in ovarian cancer (OC), as well as its effect on the malignant biological behavior of OC cells. The expression of LINC00665, miR-148b-3p, and Krüppel-like factor 5 (KLF5) in OC tissues and cells were determined by RT-qPCR. Western blot was used to detect the protein expression of KLF5. The expression patterns of LINC00665 in nuclear and cytoplasm fractions were undertaken using RT-qPCR. In addition, CCK-8 assay, clone formation assay, transwell, scratch test, and flow cytometry were respectively used to detect the cell activity, proliferation, invasiveness, healing of cells, and apoptosis rate of OC cells. Furthermore, the interactions between LINC00665 and miR-148b-3p and between miR-148b-3p and KLF5 were verified by the luciferase reporter assay, and the correlations among these three genes were analyzed. LINC00665 expression was upregulated both in OC cell lines and tissues. Si-LINC00665 inhibited cell proliferation, invasion, and migration and induced apoptosis to a certain extent. The subcellular fraction assay revealed LINC00665 to be located mainly in the cytoplasm. miR-148b-3p was a target of LINC00665, and KLF5 was directly targeted by miR-148b-3p. Si-LINC00665 inhibited KLF5 expression, miR-148b-3p inhibitor promoted KLF5 expression, and si-KLF5 inhibited LINC00665 expression. Interestingly, the expression of LINC00665 was reversely associated with miR-148b-3p expression but positively correlated with KLF5. Furthermore, miR-148b-3p expression was negatively correlated with KLF5. In addition, si-KLF5 inhibited the malignant biological behavior of OC cells, whereas miR-148b-3p inhibitor had the opposite effect. Most importantly, the si-LINC00665 could reverse the promotion effect of the miR-148b-3p inhibitor on the malignant biological behavior of OC cells. LINC00665 can be used as an effective prognostic indicator of OC, which has the potential to be a new therapeutic target.

PLGA‐PEG‐c(RGDfK)‐ Kushenol E Micelles With a Therapeutic Potential for Targeting Ovarian Cancer

Background: As a naturally derived inhibitor of autophagy, Kushenol E (KE) is a biprenylated flavonoid and is isolated from Sophora flavescens , which has been used for the treatment of cancer, hepatitis, and skin diseases. However, KE, as a poorly soluble drug, exhibited strong autophagy regulating activity in in vitro cancer cell lines, but no related studies have reported its antiovarian cancer property. Therefore, it is very beneficial to enhance the antineoplastic properties of KE by establishing an ovarian tumor‐targeting nanoparticle system modified with tumor‐homing c(RGDfK) peptides. Materials and Methods: In the current study, poly(lactic‐co‐glycolic acid)‐poly(ethylene glycol)‐modified with cyclic RGDfK peptide (PLGA‐PEG‐c(RGDfK))‐KE micelles (PPCKM) were prepared to overcome the poor water solubility of KE to meet the requirement of tumor‐active targeting. The effect of PPCKM on ovarian cancer was evaluated on SKOV‐3 cells and xenograft models in BALB/c nude mice. Results: The PPCKM showed a higher drug cumulative release ratio (82.16 ± 7.69% vs. 34.96 ± 3.05%, at 1.5 h) with good morphology, particle size (93.41 ± 2.84 nm), and entrapment efficiency (89.7% ± 1.3%). The cell viability, migration, and apoptosis analysis of SKOV‐3 cells demonstrated that PPCKM retained potent antitumor effects and promoted apoptosis at early and advanced stages with concentration‐dependent. Based on the establishment of xenograft models in BALB/c nude mice, we discovered that PPCKM reduced tumor volume and weight, inhibited proliferating cell nuclear antigen (PCNA) and Ki67 expression, as well as promoted apoptosis by targeting the tumor site. Conclusion: The findings in this study suggest that PPCKM may serve as an effective therapeutic option for ovarian cancer.