Wen Jian, Ding Yan, Zheng Shaohua, Li Xin, Xiao Ying
Department of Anesthesiology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, People's Republic of China.
Key laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China.
Cancer Biother Radiopharm. 2024 Mar;39(2):105-116. doi: 10.1089/cbr.2020.3762. Epub 2020 Sep 30.
Sevoflurane (Sev), a volatile anesthetic agent, is widely used in neurosurgery for anesthesia maintenance, accompanied with antitumor activity postanesthesia in multiple human cancers, including glioma. However, the molecular mechanism of Sev in glioma is largely unclear, including associated informative noncoding RNAs, such as long noncoding RNAs (lncRNA) and microRNAs (miRNAs). Expression of lncRNA KCNQ1 opposite strand/antisense transcript 1 (KCNQ1OT1), miRNA , and stanniocalcin-1 (STC1) was measured by real-time quantitative polymerase chain reaction and Western blotting. Cell proliferation, apoptosis, migration, and invasion were examined by 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay, fluorescence-activated cell sorting method, and transwell assays, respectively. Tumor growth was determined by xenograft models. The direct interaction between genes was confirmed by dual-luciferase reporter assay. Sev enhanced apoptotic rate, but inhibited cell viability, migration, and invasion abilities of human glioma A172 and U251 cells , as well as tumor growth inhibition . The tumor-suppressive role of Sev in glioma was accompanied with downregulated KCNQ1OT1 and STC1, and upregulated miR-146b-5p. Overexpression of KCNQ1OT1 through transfection reversed, while KCNQ1OT1 silencing aggravated the antitumor role of Sev in A172 and U251 cells. Moreover, KCNQ1OT1-mediated tumor-promoting activity in A172 and U251 cells under Sev treatment was abrogated by miR-146b-5p restoration or STC1 deletion. Essentially, KCNQ1OT1 could positively regulate STC1 by acting as miR-146b-5p decoy. KCNQ1OT1 knockdown mediated the role of Sev in glioma cell proliferation, apoptosis, migration, and invasion both and through miR-146b-5p/STC1 pathway.
七氟醚（Sev）是一种挥发性麻醉剂，在神经外科手术中广泛用于维持麻醉，在包括胶质瘤在内的多种人类癌症中，麻醉后具有抗肿瘤活性。然而，七氟醚在胶质瘤中的分子机制很大程度上尚不清楚，包括相关的信息性非编码RNA，如长链非编码RNA（lncRNA）和微小RNA（miRNA）。通过实时定量聚合酶链反应和蛋白质免疫印迹法检测lncRNA KCNQ1反义链/反义转录本1（KCNQ1OT1）、miRNA和抑钙素-1（STC1）的表达。分别通过3-(4,5-二甲基噻唑-2-基)-5-(3-羧甲氧基苯基)-2-(4-磺基苯基)-2H-四唑（MTS）法、荧光激活细胞分选法和Transwell法检测细胞增殖、凋亡、迁移和侵袭情况。通过异种移植模型确定肿瘤生长情况。通过双荧光素酶报告基因检测法证实基因之间的直接相互作用。七氟醚可提高人胶质瘤A172和U251细胞的凋亡率，但抑制其细胞活力、迁移和侵袭能力，以及抑制肿瘤生长。七氟醚在胶质瘤中的肿瘤抑制作用伴随着KCNQ1OT1和STC1的下调以及miR-146b-5p的上调。通过转染过表达KCNQ1OT1可逆转这种作用，而沉默KCNQ1OT1则会加重七氟醚在A172和U251细胞中的抗肿瘤作用。此外，恢复miR-146b-5p或缺失STC1可消除七氟醚处理下KCNQ1OT1在A172和U251细胞中介导的促肿瘤活性。从本质上讲，KCNQ1OT1可作为miR-146b-5p的诱饵正向调节STC1。敲低KCNQ1OT1通过miR-146b-5p/STC1途径介导七氟醚在胶质瘤细胞增殖、凋亡、迁移和侵袭中的作用。
