circ-NOLC1 inhibits the development of cervical cancer by regulating miR-330-5p-PALM signaling axis.

Abstract

Background: Recent studies have increasingly demonstrated that circular RNAs (circRNAs) play significant roles in the occurrence and progression of cervical cancer (CC). In CC, circRNAs act as ceRNAs by sponging miRNAs to regulate genes associated with proliferation, migration, and apoptosis, exhibiting both promoting and inhibiting effects on tumor progression. The aim of this study was to clarify the role of hsa_circ_0019686 (named circ-NOLC1) in CC.

Methods: By conducting an online GEO2R analysis of the expression profile GSE113696 in the GEO database, circ-NOLC1 was selected. The expression levels of circ-NOLC1 in CC cell lines were measured using real-time quantitative PCR (RT-qPCR). The role of circ-NOLC1 in CC was validated through both in vitro and in vivo gain-of-function assays. Bioinformatic analysis, combined with luciferase reporter and RNA Immunoprecipitation (RIP) assays, confirmed that circ-NOLC1 acts as a sponge for miR-330-5p and regulates the expression of paralemmin-1 (PALM). The role of the circ-NOLC1-miR-330-5p-PALM signaling axis in CC was elucidated through the rescue experiments. Relative gene expression levels were measured using RT-qPCR, while relative protein levels were assessed through immunohistochemistry (IHC). CCK-8, wound healing, Transwell, and flow cytometry assays were employed to evaluate CC cell proliferation, migration, and invasion, respectively.

Results: The expression levels of circ-NOLC1 were dramatically downregulated in CC cells (P < 0.001). Up-regulation of circ-NOLC1 significantly inhibited cell proliferation (P < 0.001), migration (P < 0.01) and invasion (P < 0.01), while promoting cell apoptosis (P < 0.001). In vivo studies showed that up-regulation of circ-NOLC1 suppressed tumor growth (tumor volume: P < 0.001; tumor weight: P < 0.01). Additionally, miR-330-5p was found to be up-regulated in CC (P < 0.001), whereas PALM was downregulated in CC (P < 0.001). The up-regulation of circ-NOLC1 inhibited the expression of miR-330-5p (P < 0.001) and enhanced the expression of PALM (P < 0.001). Rescue experiments further demonstrated that the up-regulation of circ-NOLC1 inhibited CC cell proliferation (P < 0.001), migration (P < 0.001), invasion (P < 0.001), while promoting apoptosis (P < 0.001) through the regulation of the miR-330-5p-PALM pathway.

Conclusion: The circ-NOLC1 inhibits CC development through regulating the miR-330-5p-PALM signaling axis. This finding reveals a novel mechanism and identifies potential therapeutic targets, emphasizing the necessity for further regulatory studies and clinical validation.