Molecular Mechanistic Analysis of the miR-503-5p/FOXK1 Signaling Axis–Mediated Promotion of Ovarian Cancer Proliferation and Invasion by LINC00273

Background Ovarian cancer is an aggressive malignancy with poor prognosis, and its molecular mechanisms remain incompletely understood. This study investigated whether LINC00273 promotes ovarian cancer cell proliferation and invasion through the miR-503-5p/ FOXK1 regulatory axis. Methods Following lentiviral-mediated overexpression of LINC00273 , the ovarian cancer OVCAR3 and PEO1 cell lines were transfected with miR-503-5p inhibitors/mimics and FOXK1 -targeting shRNA. Cell proliferation, migration, and invasion were assessed using CCK-8, colony formation, wound healing, and Transwell assays. RT-qPCR, RNA immunoprecipitation, RNA pull-down, dual-luciferase reporter assays, and Western blotting were performed to investigate the interactions among LINC00273 , miR-503-5p, and FOXK1 . Expression correlations were further analyzed in 45 paired ovarian cancer and adjacent nontumorous tissues. Results LINC00273 overexpression markedly increased ovarian cancer cell proliferation, colony formation, migration, and invasion. LINC00273 was mainly localized in the cytoplasm and acted as a competitive endogenous RNA by binding miR-503-5p. Restoration of miR-503-5p expression or FOXK1 silencing attenuated the tumor-promoting effects of LINC00273 . miR-503-5p directly targeted FOXK1 and suppressed its protein expression. Clinical samples showed reduced miR-503-5p expression, increased FOXK1 expression, and significant correlations among LINC00273 , miR-503-5p, and FOXK1 . Conclusion LINC00273 promotes malignant phenotypes of ovarian cancer cells by regulating the miR-503-5p/ FOXK1 axis. However, this study is limited by its mainly in vitro design and small clinical sample size, and further in vivo and large-cohort validation is required. Funding was provided by the Scientific Research Project of the Health Commission of Jiangsu Province (No. Z2023053), the Lianyungang Anticancer Association 2024 Municipal Cancer Prevention and Treatment Technology Development Plan Project (Grant No. ZD202407), 2024 Annual Scientific Research Approved Projects of Lianyungang City Phase VI 521 Project (Grant No. LYG065212024079), and the Project Supported by Science Foundation of Kangda College of Nanjing Medical University (Grant No. KD2024KYJJ061).