Department of Anesthesiology, Wuwei People's Hospital, North Side of Xuanwu Street, Liangzhou District, Wuwei, 733000, China.
Department of Neonatology, Wuwei People's Hospital, Wuwei, 733000, China.
Clin Transl Oncol. 2021 Sep;23(9):1866-1873. doi: 10.1007/s12094-021-02595-9. Epub 2021 Mar 27.
The aim of the present study was to elucidate the functional role of hsa-miR-328-3p/STAT3 pathway in the effects of propofol on gastric cancer proliferation.
Bioinformatics was used to analyze the molecular expression differences of hsa-miR-328-3p/STAT3 axis in stomach adenocarcinoma (n = 435) and normal samples (n = 41) from TCGA database. The expression of the above molecules in gastric cancer cells SGC-7901 and normal gastric mucosal cells GES-1 was verified via qPCR. The dual-luciferase assay was carried out to confirm the interaction between hsa-miR-328-3p and STAT3. Subsequently, the cell proliferation and the expression of the above molecules in SGC-7901 and GES-1 cells were evaluated after 10 μM propofol treatment. Finally, we analyzed whether propofol still inhibited the proliferation of gastric cancer by suppressing STAT3 pathway after hsa-miR-328-3p down-regulation.
Compared with normal samples, the expression of hsa-miR-328-3p was significantly down-regulated in stomach adenocarcinoma samples, while the expression of STAT3 and downstream target genes (MMP2, CCND1 and COX2) was up-regulated. The results were consistent with those in GES-1 and SGC-7901 cell lines. Meanwhile, we found that hsa-miR-328-3p can bind to the 3'-UTR of the potential target gene STAT3. Furthermore, propofol significantly inhibited the proliferation of gastric cancer cell line SGC-7901, where hsa-miR-328-3p was up-regulated and the expression of STAT3 and downstream proliferation-related target genes were down-regulated. However, the growth inhibition of propofol on SGC-7901 cell was significantly reversed after the inhibition of hsa-miR-328-3p.
To sum up, propofol suppressed the STAT3 pathway via up-regulating hsa-miR-328-3p to inhibit gastric cancer proliferation.
本研究旨在阐明 hsa-miR-328-3p/STAT3 通路在异丙酚对胃癌增殖作用中的功能作用。
利用生物信息学方法分析 TCGA 数据库中胃腺癌（n=435）和正常样本（n=41）中 hsa-miR-328-3p/STAT3 轴的分子表达差异。通过 qPCR 验证胃癌细胞 SGC-7901 和正常胃黏膜细胞 GES-1 中上述分子的表达。通过双荧光素酶报告基因实验证实 hsa-miR-328-3p 与 STAT3 之间的相互作用。随后，在 10 μM 异丙酚处理后评估 SGC-7901 和 GES-1 细胞中的细胞增殖和上述分子的表达。最后，在下调 hsa-miR-328-3p 后，分析异丙酚是否仍通过抑制 STAT3 通路抑制胃癌的增殖。
与正常样本相比，胃腺癌样本中 hsa-miR-328-3p 的表达明显下调，而 STAT3 和下游靶基因（MMP2、CCND1 和 COX2）的表达上调。这一结果与 GES-1 和 SGC-7901 细胞系的结果一致。同时，我们发现 hsa-miR-328-3p 可以与潜在靶基因 STAT3 的 3'-UTR 结合。此外，异丙酚显著抑制胃癌细胞系 SGC-7901 的增殖，其中 hsa-miR-328-3p 上调，STAT3 及其下游增殖相关靶基因的表达下调。然而，在抑制 hsa-miR-328-3p 后，异丙酚对 SGC-7901 细胞的生长抑制作用显著逆转。
综上所述，异丙酚通过上调 hsa-miR-328-3p 抑制 STAT3 通路抑制胃癌增殖。
