ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on gastric cancer cell malignancy by regulating the N6-methyladenosine modification of the lncRNA DLX6-AS1.

Sevoflurane, an inhalation anesthetic, has been shown to suppress cancer development. In this study, we investigated the specific mechanisms involving sevoflurane, zinc-finger CCCH-type containing 13 (ZC3H13), and lncRNA DLX6-AS1 in gastric cancer (GC) progression, focusing on the N6-methyladenosine (mA) modification of long non-coding RNAs (lncRNAs). We used quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analyses to measure the levels of ZC3H13 and lncRNA DLX6-AS1 in GC tissues and cells. Furthermore, we conducted Cell Counting Kit-8, colony formation, Transwell, and tumor xenograft assays to evaluate changes in GC cell malignancy following cell transfection and sevoflurane treatment. Additionally, actinomycin D, methylated RNA immunoprecipitation, and qRT-PCR assays were performed to examine the regulatory effects of ZC3H13 on the DLX6-AS1 mA modification. We detected elevated levels of ZC3H13 in GC samples, while ZC3H13 silencing inhibited GC cell proliferation, migration, and invasion. Silencing ZC3H13 also enhanced the inhibitory effects of sevoflurane on GC cell malignancy. Moreover, we found that the increased expression of DLX6-AS1 in GC cells could be suppressed by ZC3H13 through the mediation of the mA modification of DLX6-AS1, thereby reducing DLX6-AS1 stability. In conclusion, ZC3H13 knockdown enhances the inhibitory effect of sevoflurane on GC cell malignancy by inducing DLX6-AS1 mA modification. Our findings may help identify potential therapeutic targets for the treatment of GC.