DEAH-box 多肽 32 通过激活β-catenin 通路促进肝细胞癌进展。
DEAH-box polypeptide 32 promotes hepatocellular carcinoma progression via activating the β-catenin pathway.
机构信息
State Key Laboratory of Organ Failure Research, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Department of Infectious Diseases and Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
出版信息
Ann Med. 2021 Dec;53(1):437-447. doi: 10.1080/07853890.2021.1898674.
PURPOSE
Hepatocellular carcinoma (HCC) is refractory cancer with high morbidity and high mortality. DEAH-box polypeptide 32 (DHX32) was upregulated in several types of malignancies and predicted poor prognosis. Herein, we investigated the role of DHX32 in HCC progression.
METHODS
The expression of DHX32, β-catenin, and epithelial-mesenchymal transition (EMT)-related makers were determined by Western blot and quantitative real-time PCR assays. Cell proliferation was tested by EdU cell proliferation assay. The effect of DHX32 and β-catenin on cell migration and invasion were detected by wound-healing and Traswell invasion assays. Tumour xenografts were performed to determine the effect of DHX32 on HCC tumour growth.
RESULTS
High level of DHX32 expression was associated with reduced overall survival in HCC patients. DHX32 expression was upregulated in human HCC cells and ectopic expression of DHX32 induced EMT, promoted the mobility and proliferation of HCC cells, and enhanced tumour growth . Silencing DHX32 reversed EMT, inhibited the malignancy behaviors of HCC cells, and suppressed tumour growth. Mechanistically, silencing DHX32 decreased the expression of β-cateninin in nucleus and β-catenin siRNA abrogated DHX32-mediated HCC progression.
CONCLUSION
DHX32 was an attractive regulator of HCC progression and indicated DHX32 canserve as a potential biomarker and therapeutic target for HCC patients.
目的
肝细胞癌（HCC）是一种难治性癌症，具有高发病率和高死亡率。DEAH -box 多肽 32（DHX32）在几种类型的恶性肿瘤中上调，并预测预后不良。在此，我们研究了 DHX32 在 HCC 进展中的作用。
方法
通过 Western blot 和定量实时 PCR 检测 DHX32、β-连环蛋白和上皮间质转化（EMT）相关标志物的表达。通过 EdU 细胞增殖试验检测细胞增殖。通过划痕愈合和 Transwell 侵袭试验检测 DHX32 和 β-连环蛋白对细胞迁移和侵袭的影响。进行肿瘤异种移植以确定 DHX32 对 HCC 肿瘤生长的影响。
结果
DHX32 高表达与 HCC 患者总体生存率降低相关。DHX32 在人 HCC 细胞中表达上调，异位表达 DHX32 诱导 EMT，促进 HCC 细胞的迁移和增殖，并增强肿瘤生长。沉默 DHX32 逆转 EMT，抑制 HCC 细胞的恶性行为，并抑制肿瘤生长。机制上，沉默 DHX32 降低了核内β-连环蛋白的表达，而β-连环蛋白 siRNA 则阻断了 DHX32 介导的 HCC 进展。
结论
DHX32 是 HCC 进展的一个有吸引力的调节剂，并表明 DHX32 可以作为 HCC 患者的潜在生物标志物和治疗靶点。
Zotero 插件