RASA4 inhibits the HIFα signaling pathway to suppress proliferation of cervical cancer cells.
RASA4 inhibits the HIFα signaling pathway to suppress proliferation of cervical cancer cells.
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RASA4抑制HIFα信号通路抑制宫颈癌细胞增殖
DOI：
10.1080/21655979.2021.2002499
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发表时间：
2021-12
期刊：
影响因子：
4.9
通讯作者：
Xu W
中科院分区：
文献类型：
--
作者：
Chen J;Huang J;Huang Q;Li J;Chen E;Xu W
RAS p21蛋白激活因子4（RASA 4）被认为是一种Ca 2+促进的Ras-MAPK通路抑制剂，可抑制肿瘤生长。然而，RASA 4在宫颈鳞状细胞癌（CESC）中的作用仍不清楚。使用GEO和GEPIA数据库分析RASA 4的mRNA水平。进行Kaplan-Meier分析和ROC分析，以确定TCGA-SCE队列患者的预后和诊断价值。进行CCK 8和集落测定以评估RASA 4异位表达和基因失活对肿瘤细胞增殖的影响。进行了体内实验。采用荧光素酶报告基因分析和HIFα抑制剂LW 6验证RASA 4与HIF α信号通路之间的调控关系。GEPIA和GEO数据库分析表明RASA 4在CESC组织中的表达相对于在非癌组织中的表达较低。基于TCGA数据库，低表达RASA 4表示高预后和诊断价值。异位表达RASA 4减弱了HeLa细胞的增殖潜力，而RASA 4基因失活在HeLa和C-33 A细胞中产生相反的影响。RASA 4缺陷对肿瘤发生的促进作用也在体内记录。随后，RASA 4负调控HIFα驱动的荧光素酶活性，减弱survivin的表达。同时，LW 6处理消除了HeLa细胞的增殖增加，以及RASA 4耗竭引起的生存素表达增加。我们的研究结果表明，RASA 4可以通过抑制HIFα信号通路抑制宫颈癌细胞的增殖，这为CESC的靶向治疗提供了新的前景。
RAS p21 protein activator 4 (RASA4) has been recognized as a Ca2+-promoted Ras–MAPK pathway suppressor that inhibits tumor growth. However, the role of RASA4 in cervical squamous cell carcinoma (CESC) remains unclear. The mRNA levels of RASA4 were analyzed using the GEO and GEPIA databases. Kaplan–Meier analysis and ROC analyses were conducted to determine the prognostic and diagnostic values for patients from the TCGA-CSCE cohort. The CCK8 and colony assays were performed to assess the impact of RASA4 ectopic expression and gene inactivation on tumor cell proliferation. In vivo experiments were performed. Luciferase reporter assays and LW6 (a HIFα inhibitor) were employed to verify the regulatory relationship between RASA4 and the HIFa signaling pathway. The GEPIA and GEO database analysis demonstrated poorly expressed RASA4 in the CESC tissues relative to that in the noncancerous tissues. Based on the TCGA database, poorly expressed RASA4 signified high prognostic and diagnostic values. Ectopically expressed RASA4 weakened the proliferative potential of HeLa cells, whereas RASA4 genetic inactivation produced the opposite impact in the HeLa and C-33A cells. The promoting effect of RASA4 deficiency on tumourigenesis was also recorded in vivo. Subsequently, RASA4 negatively regulated the HIFα-driven luciferase activities and weakened the expression of survivin. Meanwhile, LW6 treatment abrogated the increased proliferation of HeLa cells, as well as the increased expression of survivin by RASA4 depletion. Our findings indicated that RASA4 can inhibit the proliferation of cervical cancer cells by inactivating the HIFα signaling pathway, suggesting novel prospects for targeted therapy against CESC.
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影响因子：
5.2
作者：
Wang, Yan;Qi, Yan-Xiang;Tsang, Suk-Ying
通讯作者：
Tsang, Suk-Ying
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影响因子：
5.4
作者：
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通讯作者：
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DOI：
10.26355/eurrev_201711_13817
发表时间：
2017-11-01
影响因子：
3.3
作者：
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通讯作者：
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影响因子：
3.7
作者：
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通讯作者：
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影响因子：
7.3
作者：
Zhou, Bingying;Der, Channing J.;Cox, Adrienne D.
通讯作者：
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