摘要
丝裂原活化蛋白激酶(MAPK)家族在基因表达调控和细胞功能活动中发挥了关键作用,并且在肿瘤的发生发展中也起着重要作用。最近发现,MAPK家族的一个新成员MAPK4在肺癌的进展中起着重要作用,然而MAPK4在宫颈癌中的作用尚未见报道。本研究首先通过GSCA在线软件在12个组织类型共65种肿瘤细胞系中分析了MAPK4的mRNA水平。根据分析的结果,选取了宫颈癌细胞中MAPK4表达最高的HeLa细胞和表达最低的SiHa细胞作为研究模型进行下一步的研究。在HeLa细胞中,干扰MAPK4的表达后,通过CCK8试验检测了宫颈癌细胞的增殖能力,发现HeLa细胞的增殖能力显著下降。在SiHa细胞中,转染MAPK4过表达质粒后检测细胞的增殖能力,发现MAPK4过表达后,SiHa细胞的增殖能力显著上升。最后,本研究探索了MAPK4诱导宫颈癌细胞增殖的分子机制,发现在宫颈癌细胞中MAPK4促进了蛋白激酶B(AKT)的活性,这表明MAPK4可能通过激活AKT促进了宫颈癌细胞的增殖。上述研究结果表明,MAPK4能作为判断宫颈癌增殖潜能的标志物以及宫颈癌治疗的潜在分子靶点。本研究为宫颈癌的发病机制提供了新的见解,对开发新的靶向药物治疗宫颈癌具有一定的价值。
Abstract
Mitogenactivated protein kinase(MAPK) family plays a key role in the regulation of gene expression and cytoplasmic function, and also plays an important role in the development of tumor. Recently, MAPK4, a novel member of MAPK family, has been found to promote the progression of lung cancer. However, the role of MAPK4 has not been reported in cervical cancer. In this study, we first analyzed MAPK4 mRNA levels in 65 tumor cell lines from 12 tissue types by GSCA online software. We found MAPK4 was highly expressed in HeLa cells. The MAPK4 levels were lower in SiHa cells relative to HeLa cells. And then these two cervical cancer cells were selected for further study. Firstly, the MAPK4 levels were depleted in HeLa cells, and then the proliferation ability of HeLa cells was detected by CCK8 assay. We found that depletion of MAPK4 significantly decreased the proliferation ability of HeLa cells. Next, MAPK4 overexpression plasmids were transfected in SiHa cells, and then cell proliferation was detected. We found that MAPK4 overexpression significantly increased the cell viability of SiHa cells. Moreover, we explored the molecular mechanism of MAPK4 induced proliferation of cervical cancer cells. By Western blot, we showed that MAPK4 promoted AKT activity in both cervical cancer cells. These results suggested that MAPK4 might promote the proliferation of cervical cancer cells by activating AKT. In conclusion, our results showed that MAPK4 could be used as a marker of cervical cancer proliferation potential and a potential molecular target for cervical cancer treatment. This study provided new insights for the pathogenesis of cervical cancer, and exerted a certain value for the development of new targeted drugs for the treatment of cervical cancer.
赖丽梨,段华英,邹争志.
丝裂原活化蛋白激酶4通过激活AKT促进宫颈癌细胞增殖[J]. 激光生物学报. 2020, 29(3): 231-236
Mitogenactivated Protein Kinase 4 Promotes Cell Proliferation by #br#
Activating AKT in Cervical Cancer Cells[J]. Acta Laser Biology Sinica. 2020, 29(3): 231-236
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