Jiangsu Province Engineering Research Center for Cardiovascular and Cerebrovascular Disease and Cancer Prevention and Control, Jiangsu Vocational College of Medicine, Yancheng, China.
Science and Technology Department, Jiangsu Vocational College of Medicine, Yancheng, China.
DNA Cell Biol. 2024 Nov;43(11):559-569. doi: 10.1089/dna.2024.0107. Epub 2024 Oct 15.
Previous findings have indicated a marked upregulation of SNORA71A in gallbladder cancer (GBC) tissues compared to normal samples. However, the precise role and molecular mechanisms of SNORA71A in GBC remain largely unknown. Moreover, gemcitabine (GEM) drug resistance has been found to lead to unfavorable outcomes and recurrence in GBC patients. Therefore, this study aims to investigate the impact of SNORA71A on GBC and explore its potential effects on the sensitivity of GBC cells to GEM. RT-qPCR was conducted to assess SNORA71A level in matched normal and GBC tissues. Cell proliferation was examined through CCK-8 and 5-ethynyl-2'-deoxyuridine (EdU) assays. Additionally, the expression of proteins in GBC cells was analyzed using western blot assay. The level of SNORA71A was notably higher in GBC tissues relative to normal tissues. SNORA71A overexpression led to increased GBC cell proliferation and invasion. Conversely, SNORA71A deficiency strongly suppressed GBC cell proliferation and invasion and triggered cell apoptosis and ferroptosis. Additionally, downregulation of SNORA71A obviously enhanced the antiproliferative and anti-invasive effects of GEM on GBC cells, whereas these changes were reversed by inhibiting ferroptosis. Furthermore, deficiency of SNORA71A further augmented the GEM-induced downregulation of p-Akt, Nrf2, and GPX4 in NOZ cells; however, these effects were reversed by ferroptosis inhibition. Collectively, these findings suggested that downregulation of SNORA71A may increase the sensitivity of GBC cells to GEM by triggering ferroptosis through inhibiting the AKT/NRF2/GPX4 signaling pathway.
先前的研究结果表明，胆囊癌（GBC）组织中 SNORA71A 的表达明显上调，与正常样本相比。然而，SNORA71A 在 GBC 中的确切作用和分子机制在很大程度上仍然未知。此外，已经发现吉西他滨（GEM）耐药导致 GBC 患者预后不良和复发。因此，本研究旨在探讨 SNORA71A 对 GBC 的影响，并探索其对 GBC 细胞对 GEM 敏感性的潜在影响。通过 RT-qPCR 评估匹配的正常和 GBC 组织中的 SNORA71A 水平。通过 CCK-8 和 5-乙炔基-2'-脱氧尿苷（EdU）测定法检查 GBC 细胞的增殖情况。此外，使用 Western blot 测定法分析 GBC 细胞中的蛋白质表达。SNORA71A 在 GBC 组织中的水平明显高于正常组织。SNORA71A 的过表达导致 GBC 细胞增殖和侵袭增加。相反，SNORA71A 的缺乏强烈抑制 GBC 细胞的增殖和侵袭，并触发细胞凋亡和铁死亡。此外，SNORA71A 的下调明显增强了 GEM 对 GBC 细胞的抗增殖和抗侵袭作用，而这些变化通过抑制铁死亡而逆转。此外，SNORA71A 的缺乏进一步增强了 GEM 诱导的 NOZ 细胞中 p-Akt、Nrf2 和 GPX4 的下调；然而，这些效应通过铁死亡抑制而逆转。总之，这些发现表明，通过抑制 AKT/NRF2/GPX4 信号通路触发铁死亡，下调 SNORA71A 可能增加 GBC 细胞对 GEM 的敏感性。
