Jiang Longchang, Hu Liangbiao George
Translational Safety and Bioanalytical Sciences, Amgen Research, Amgen Asia Research and Development Center, Shanghai 201210, P.R. China.
Oncol Lett. 2020 Dec;20(6):278. doi: 10.3892/ol.2020.12141. Epub 2020 Sep 23.
Gastric cancer is the second most common cause of cancer-associated death in Asia. The incidence and mortality rates of gastric cancer have markedly increased in the past few decades. Therefore, the identification of novel gastric cancer biomarkers are needed to determine prognosis. The role of serpin peptidase inhibitor clade A member 1 (SERPINA1) has been studied in several types of cancer; however, little is known about its mechanism in gastric cancer. The present study aimed to evaluate as a potential prognostic biomarker in gastric cancer and to identify the possible mechanisms underlying its action. The expression levels of in several gastric cancer datasets were assessed, and it was identified that high expression of was associated to poor clinical outcomes. Furthermore, using histochemical analysis, western blotting, apoptotic analysis, gap closure and invasion assays in cell lines, it was reported that silencing of inhibited the formation of cellular pseudopodia and did not affect apoptosis, but promoted cell cycle S-phase entry. In addition, overexpression of increased the migration and invasion of gastric cancer cells, whereas knockdown of decreased these functions. Moreover, SERPINA1 overexpression increased the protein levels of SMAD4, which is a key regulator of the transforming growth factor (TGF)-β signaling pathway. Taken together, the present data demonstrated that SERPINA1 promotes gastric cancer progression through TGF-β signaling, and suggested that may be a novel prognostic biomarker from tumor tissue biopsy in gastric cancer.
胃癌是亚洲癌症相关死亡的第二大常见原因。在过去几十年中，胃癌的发病率和死亡率显著上升。因此，需要鉴定新的胃癌生物标志物以确定预后。丝氨酸蛋白酶抑制剂A家族成员1（SERPINA1）在几种癌症类型中的作用已得到研究；然而，其在胃癌中的机制尚不清楚。本研究旨在评估其作为胃癌潜在预后生物标志物的作用，并确定其作用的潜在机制。评估了几种胃癌数据集中的表达水平，发现高表达与不良临床结果相关。此外，通过组织化学分析、蛋白质印迹、细胞凋亡分析、细胞间隙闭合和侵袭试验，据报道，沉默可抑制细胞伪足的形成，不影响细胞凋亡，但促进细胞周期S期进入。此外，的过表达增加了胃癌细胞的迁移和侵袭，而敲低则降低了这些功能。此外，SERPINA1过表达增加了SMAD4的蛋白水平，SMAD4是转化生长因子（TGF）-β信号通路的关键调节因子。综上所述，目前的数据表明SERPINA1通过TGF-β信号通路促进胃癌进展，并提示可能是胃癌肿瘤组织活检的一种新的预后生物标志物。
