Liu Chundong, Chen Zeguang
Department of Anesthesiology, Wuhan Fourth Hospital, Wuhan 430033, Hubei, China.
Operating Room, Wuhan Fourth Hospital, Wuhan 430033, Hubei, China.
Heliyon. 2024 Aug 2;10(16):e35722. doi: 10.1016/j.heliyon.2024.e35722. eCollection 2024 Aug 30.
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.
七氟烷是一种吸入性麻醉剂，已被证明可抑制癌症发展。在本研究中，我们研究了七氟烷、含锌指CCCH型结构域13（ZC3H13）和长链非编码RNA DLX6-AS1在胃癌（GC）进展中的具体机制，重点关注长链非编码RNA（lncRNAs）的N6-甲基腺苷（m⁶A）修饰。我们使用定量实时聚合酶链反应（qRT-PCR）和蛋白质免疫印迹分析来测量GC组织和细胞中ZC3H13和lncRNA DLX6-AS1的水平。此外，我们进行了细胞计数试剂盒-8、集落形成、Transwell和肿瘤异种移植试验，以评估细胞转染和七氟烷处理后GC细胞恶性程度的变化。此外，还进行了放线菌素D、甲基化RNA免疫沉淀和qRT-PCR试验，以检测ZC3H13对DLX6-AS1 m⁶A修饰的调控作用。我们检测到GC样本中ZC3H13水平升高，而ZC3H13沉默可抑制GC细胞增殖、迁移和侵袭。沉默ZC3H13还增强了七氟烷对GC细胞恶性程度的抑制作用。此外，我们发现ZC3H13可通过介导DLX6-AS1的m⁶A修饰抑制GC细胞中DLX6-AS1的表达增加，从而降低DLX6-AS1的稳定性。总之，敲低ZC3H13可通过诱导DLX6-AS1 m⁶A修饰增强七氟烷对GC细胞恶性程度的抑制作用。我们的研究结果可能有助于确定GC治疗的潜在靶点。
