Ropivacaine Retards the Viability, Migration, and Invasion of Choriocarcinoma Cells by Regulating the Long Noncoding RNA OGFRP1/MicroRNA-4731-5p/HIF3A Axis.

Abstract

Choriocarcinoma is an aggressive gestational trophoblastic neoplasm. This study attempted to explore the biological functions and underlying mechanisms by which ropivacaine restrains the progression of choriocarcinoma. The expression of long noncoding RNA OGFRP1, microRNA-4731-5p (miR-4731-5p), and HIF3A in choriocarcinoma cells was assessed by qRT-PCR. Choriocarcinoma cells treated with ropivacaine at the concentration of 100, 500, and 1000μM were cultured for 24, 48, and 72h, respectively. Choriocarcinoma cell viability was evaluated by MTT assay. Transwell assay was conducted to examine choriocarcinoma cell migration and invasion. Additionally, the target relationship between OGFRP1 and miR-4731-5p or between miR-4731-5p and HIF3A was predicted by bioinformatics analysis and confirmed by dual-luciferase reporter assays. OGFRP1 and HIF3A expression were enhanced in choriocarcinoma cells, while miR-4731-5p expression was inhibited. Treatment with ropivacaine impeded choriocarcinoma cell viability, migration, and invasion. Choriocarcinoma cells treated with 1000μM ropivacaine for 48h were selected for subsequent experiments. OGFRP1 elevation or miR-4731-5p deficiency mitigated the reduction effect of ropivacaine on tumorigenesis of choriocarcinoma cells. Besides, miR-4731-5p was predicted as the potential OGFRP1 target by StarBase and LncBase, and HIF3A was predicted as the potential miR-4731-5p target by StarBase and TargetScan. Dual-luciferase reporter assays determined that miR-4731-5p was a target of OGFRP1 and HIF3A was a target of miR-4731-5p. Feedback experiments declared that miR-4731-5p elevation or HIF3A suppression reversed the promoting effect of OGFRP1 overexpression on the malignant behaviors of ropivacaine-treated choriocarcinoma cells. Ropivacaine constrained choriocarcinoma cell viability, migration, and invasion through modulating the OGFRP1/miR-4731-5p/HIF3A axis. Our study may provide a novel strategy for choriocarcinoma prevention and treatment.