CircATXN7 regulates the proliferation and invasion of esophageal cancer cells through miR-4319/NLRC5

Abstract

Background

This study aimed to explore the molecular mechanism through which circular RNA of ataxin 7 (circATXN7) regulates the proliferation and invasion of esophageal cancer (EC) cells via microRNA (miR)-4319/NLR family CARD domain containing 5 (NLRC5).

Methods

The localization of circATXN7 in EC cells was determined by RNA fluorescent in situ hybridization (RNA-FISH). The mRNA levels of circATXN7, miR-4319, and NLRC5 were quantified by reverse transcription-polymerase chain reactions. The binding activity of circATXN7 to miR-4319 was assessed using RNA-binding protein immunoprecipitation. Whether circATXN7 regulates the proliferation of EC cells via miR-4319 was explored using dual-luciferase reporter gene colony formation assays. Protein levels were quantified by western blot. The effect of NLRC5 on the proliferation and invasion of EC cells was examined using colony formation and Transwell assays. A subcutaneous transplanted tumor nude mouse model was established to observe the effect of circATXN7 on the proliferation of EC cells in vivo.

Results

circATXN7 localized mainly to the cytoplasm. Overexpression or inhibition of miR-4319 significantly regulated the proliferation of EC cells, while circATXN7 competitively inhibited miR-4319 expression. Overexpression of miR-4319 significantly inhibited NLRC5 expression, indicating NLRC5 is a downstream regulatory target of miR-4319. circATXN7 influenced NLRC5 expression via miR-4319. In vivo tumor formation experiments in nude mice revealed that knocking down circATXN7 regulated NLRC5 expression via miR-4319 and significantly inhibited the proliferation of EC cells.

Conclusions

In vitro cell and in vivo animal experiments showed that circATXN7 regulates the proliferation, invasion, and migration of EC cells through the miR-4319/NLRC5 signaling pathway.