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长链非编码 RNA MNX1-AS1 通过激活 MAPK 通路促进宫颈癌的进展。

LncRNA MNX1-AS1 promotes the progression of cervical cancer through activating MAPK pathway.

机构信息

Department of Obstetrics and Gynecology, The First People's Hospital of Wenling, Wenling, Zhejiang, China.

出版信息

J Cell Biochem. 2019 Mar;120(3):4268-4277. doi: 10.1002/jcb.27712. Epub 2018 Oct 9.

Abstract

Long noncoding RNAs (lncRNAs) have been discovered as significant regulators in a wide range of human cancers. Among them, lncRNA MNX1-AS1 has been proved to be an oncogene in ovarian cancer and glioblastoma. However, the regulatory mechanism of MNX1-AS1 in cervical cancer remains to be understood. Therefore, this study planned to explore the role of MNX1-AS1 in cervical cancer. In the beginning, we found that the expression of MNX1-AS1 was obviously upregulated in cervical cancer tissues and cell lines. Kaplan-Meier survival analysis revealed that patients with higher MNX1-AS1 expression level suffered from shorter overall survival time than those with lower MNX1-AS1 level. Moreover, by loss-of-function and gain-of-function assay, the effect of MNX1-AS1 on cell proliferation and apoptosis was examined on cellular level. Results showed that the proliferation of Hela cells was significantly inhibited and apoptosis enhanced by the transfection of shMNX1-AS1, while overexpressing MNX1-AS1 in E6E7 cells presented the contrary results. As for mechanism investigation, it was demonstrated that overexpression of MNX1-AS1 significantly improved the expression of p-ERK1/2 and p-JNK. And the effects of MNX1-AS1 on cell proliferation and apoptosis would be diminished after inactivating the phosphorylation of either ERK or JNK. Taken together, it was identified that MNX1-AS1 promoted proliferation and inhibited apoptosis of cervical cancer cells through MAPK pathway.

摘要

长链非编码 RNA(lncRNA)已被发现是广泛存在于人类癌症中的重要调控因子。其中,lncRNA MNX1-AS1 已被证明在卵巢癌和胶质母细胞瘤中是一种癌基因。然而,MNX1-AS1 在宫颈癌中的调控机制仍有待了解。因此,本研究计划探讨 MNX1-AS1 在宫颈癌中的作用。首先,我们发现 MNX1-AS1 在宫颈癌组织和细胞系中的表达明显上调。Kaplan-Meier 生存分析显示,MNX1-AS1 表达水平较高的患者总生存时间短于 MNX1-AS1 水平较低的患者。此外,通过功能丧失和功能获得实验,在细胞水平上检测了 MNX1-AS1 对细胞增殖和凋亡的影响。结果表明,shMNX1-AS1 转染可显著抑制 Hela 细胞的增殖并促进其凋亡,而过表达 MNX1-AS1 在 E6E7 细胞中则呈现相反的结果。关于机制研究,结果表明 MNX1-AS1 的过表达显著改善了 p-ERK1/2 和 p-JNK 的表达。而 ERK 或 JNK 的磷酸化失活后,MNX1-AS1 对细胞增殖和凋亡的影响会减弱。综上所述,MNX1-AS1 通过 MAPK 通路促进宫颈癌细胞的增殖并抑制其凋亡。

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