Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215000, P.R. China.
Department of Infectious Diseases, The Second Affiliated Hospital and Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325027, P.R. China.
Mol Med Rep. 2018 Mar;17(3):4633-4638. doi: 10.3892/mmr.2018.8400. Epub 2018 Jan 9.
Gastric cancer is the most common type of gastrointestinal cancer, causing mortality worldwide. However, the underlying molecular mechanism in gastric cancer progression remains unclear. The autophagic flux was determined in gastric cancer cells overexpressing or inhibiting Sp1 transcription factor (SP1) using western blotting, reverse transcription‑polymerase chain reaction and immunofluorescence staining. Luciferase and ChIP assays were performed to detect the potential underlying mechanism of SP1 in gastric cancer cells. Lastly, immunohistochemistry was also performed on SP1 and p62 expression levels in human gastric cancer specimens. It was demonstrated that SP1 diminished autophagic flux via activating p62 in gastric cancer. Moreover, SP1 deficiency increased the rate of autophagy of gastric cancer cells. Notably, it was observed that SP1 enhanced the expression levels of p62 by directly binding to the promoter of p62. Analysis of gastric cancer specimen staining established that p62 expression levels were increased in SP1‑positve gastric tissues. The present study provided evidence for a novel mechanism regulating autophagy in gastric cancer cells.
胃癌是最常见的胃肠道癌症类型，在全球范围内导致死亡率升高。然而，胃癌进展中潜在的分子机制仍不清楚。使用 Western blot、逆转录-聚合酶链反应和免疫荧光染色法测定过表达或抑制 Sp1 转录因子 (SP1) 的胃癌细胞中的自噬通量。进行荧光素酶和 ChIP 测定以检测 SP1 在胃癌细胞中的潜在作用机制。最后，对人胃癌标本中的 SP1 和 p62 表达水平进行免疫组织化学分析。结果表明，SP1 通过激活胃癌中的 p62 来减少自噬通量。此外，SP1 缺乏会增加胃癌细胞的自噬率。值得注意的是，观察到 SP1 通过直接结合 p62 的启动子增强 p62 的表达水平。对胃癌标本染色的分析表明，SP1 阳性的胃癌组织中 p62 的表达水平增加。本研究为调节胃癌细胞自噬的新机制提供了证据。
