Gu Shudong, Zhang Shu, Huang Hua, Wang Qingqing, Fan Haowen, Shao Qi, Mao Guoxin, Qian Li
Department of Oncology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Department of Pathology, Affiliated Hospital of Nantong University, Nantong 226001, China.
Transl Cancer Res. 2020 Apr;9(4):2672-2682. doi: 10.21037/tcr.2020.02.69.
HAX-1 is involved in the regulation of cellular processes such as apoptosis, proliferation and migration and is closely related to tumorigenesis and tumor metastasis. However, expression of HAX-1 in gastric cancer and its role in tumor development and progression remain unclear.
Quantitative polymerase chain reaction was used to detect the expression of HAX-1 mRNA in gastric cancer tissues and adjacent non-tumorous tissues. Expression of HAX-1, caspase-3 and caspase-9 was detected by immunohistochemistry in gastric cancer. Small hairpin RNA (shRNA) plasmid was employed to establish SGC-7901 cell lines that expressed HAX-1 at low levels. The effect of HAX-1 expression on cell proliferation will be studied at the cell level.
Quantitative polymerase chain reaction (qPCR) showed HAX-1 mRNA expression to be significantly upregulated in gastric cancer tissues. Based on immunohistochemical analysis, upregulation of HAX-1 protein expression correlates positively with the degree of tumor differentiation, vascular tumor thrombus, tumor-node-metastasis stage and lymph node metastatic status and negatively with expression of the apoptosis-related proteins caspase-3 and caspase-9. In addition, high HAX-1 protein expression indicates a poor prognosis. Serum starvation-release experiments revealed that HAX-1 promotes the proliferation of SGC-7901 gastric cancer cells; as cell proliferation increased, expression of HAX-1 also increased, whereas the expression levels of the apoptosis-related proteins caspase-3 and caspase-9 decreased. HAX-1 siRNA transfection experiments demonstrated that HAX-1 gene knockdown causes cell cycle arrest at the G0/G1 phase, inhibits proliferation, and downregulates HAX-1 expression while enhancing expression of apoptosis-related proteins.
HAX-1 might exert its proliferation-promoting and anti-apoptotic effects by inhibiting expression of the apoptosis-related proteins caspase-3 and caspase-9.HAX-1 may be a potential target for the treatment of gastric cancer.
HAX-1参与细胞凋亡、增殖和迁移等细胞过程的调控，与肿瘤发生和肿瘤转移密切相关。然而，HAX-1在胃癌中的表达及其在肿瘤发生发展中的作用仍不清楚。
采用定量聚合酶链反应检测胃癌组织及癌旁非肿瘤组织中HAX-1 mRNA的表达。通过免疫组织化学检测胃癌中HAX-1、半胱天冬酶-3和半胱天冬酶-9的表达。采用小发夹RNA（shRNA）质粒建立低表达HAX-1的SGC-7901细胞系。在细胞水平研究HAX-1表达对细胞增殖的影响。
定量聚合酶链反应（qPCR）显示，胃癌组织中HAX-1 mRNA表达显著上调。基于免疫组织化学分析，HAX-1蛋白表达上调与肿瘤分化程度、肿瘤血管血栓、肿瘤-淋巴结-转移分期和淋巴结转移状态呈正相关，与凋亡相关蛋白半胱天冬酶-3和半胱天冬酶-9的表达呈负相关。此外，HAX-1蛋白高表达提示预后不良。血清饥饿-再释放实验表明，HAX-1促进SGC-7901胃癌细胞增殖；随着细胞增殖增加，HAX-1表达也增加，而凋亡相关蛋白半胱天冬酶-3和半胱天冬酶-9的表达水平降低。HAX-1 siRNA转染实验表明，HAX-基因敲低导致细胞周期停滞在G0/G1期，抑制增殖，下调HAX-1表达，同时增强凋亡相关蛋白的表达。
HAX-1可能通过抑制凋亡相关蛋白半胱天冬酶-3和半胱天冬酶-9的表达发挥其促增殖和抗凋亡作用。HAX-1可能是胃癌治疗的潜在靶点。
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