LncRNA MNX1-AS1 promotes the progression of cervical cancer through activating MAPK pathway
LncRNA MNX1-AS1 promotes the progression of cervical cancer through activating MAPK pathway
复制标题
DOI：
10.1002/jcb.27712
复制
发表时间：
2019-03-01
影响因子：
4
通讯作者：
Zheng, Meiyun
中科院分区：
文献类型：
--
作者：
Liu, Xiang;Yang, Qian;Zheng, Meiyun
长非编码RNA(LncRNAs)已被发现在多种人类癌症中具有重要的调节作用。其中，LncRNA MNX1-AS1已被证实是卵巢癌和胶质母细胞瘤中的癌基因。然而，MNX1-AS1在宫颈癌中的调控机制尚不清楚。因此，本研究拟探讨MNX1-AS1在宫颈癌中的作用。最初，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表达水平高的患者总体生存时间短于MNX1-AS1表达水平低的患者。此外，通过功能丧失和功能获得实验，从细胞水平检测MNX1-AS1对细胞增殖和凋亡的影响。结果表明，shMNX1-AS1基因可显著抑制Hela细胞的增殖，促进细胞凋亡，而过表达MNX1-AS1基因的E6E7细胞则相反。在机制研究方面，MNX1-AS1过表达显著提高了p-ERK1/2和p-JNK的表达。失活ERK或JNK的磷酸化后，MNX1-AS1对细胞增殖和凋亡的作用减弱。综上所述，MNX1-AS1通过MAPK途径促进宫颈癌细胞增殖，抑制细胞凋亡。
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.