长链非编码RNA MIR99AHG通过miR577/FOXP1轴诱导上皮-间质转化并抑制细胞凋亡，从而促进胃癌进展。

Long noncoding RNA MIR99AHG promotes gastric cancer progression by inducing EMT and inhibiting apoptosis via miR577/FOXP1 axis.

作者信息

Meng Qingyang, Wang Xiangjun, Xue Tongqing, Zhao Qiangfang, Wang Wei, Zhao Kun

机构信息

Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, China.

出版信息

Cancer Cell Int. 2020 Aug 27;20:414. doi: 10.1186/s12935-020-01510-6. eCollection 2020.

BACKGROUND

Long non-coding RNAs (lncRNAs) play a vital role in the genesis and development of human cancer. LncRNA MIR99AHG has been reported to be upregulated in acute myeloid leukemia (AML); however, its function in gastric cancer (GC) is still not clear. Here we were aiming to screen the prognostic lncRNA candidates and to explore the function of MIR99AHG in GC.

METHODS

We have preliminarily screened some candidate lncRNA biomarkers in GC tissues through analyzing microarray datasets. The expression level of MIR99AHG in GC cell lines and tissues was monitored via qPCR. Survival analysis was performed with the patients of our hospital and TCGA database cases. CCK-8 assay, trans-well assay and flow cytometry were performed to determine cell proliferation, invasion, migration and apoptosis. Meanwhile, a target of MIR99AHG was predicted and identified by luciferase reporter gene detection experiments.

RESULTS

MIR99AHG was strongly up-regulated in human GC and contributed to cancer progression. Kaplan-Meier analysis revealed that up-regulating MIR99AHG expression was positively correlated with unfavorable overall survival (P < 0.01) of patients from our hospital and TCGA database. Knockdown of MIR99AHG expression inhibited cell proliferation, invasion, migration and promoted cell apoptosis. Moreover, MIR99AHG worked as an oncogenic gene though competing for endogenous RNA (ceRNA) of miR-577.

CONCLUSIONS

Our findings suggested that MIR99AHG contributes to malignant phenotypes of GC and may become a promising therapeutic target.

背景

长链非编码RNA（lncRNAs）在人类癌症的发生和发展中起着至关重要的作用。据报道，lncRNA MIR99AHG在急性髓系白血病（AML）中上调；然而，其在胃癌（GC）中的功能仍不清楚。在此，我们旨在筛选预后lncRNA候选物，并探索MIR99AHG在GC中的功能。

方法

我们通过分析微阵列数据集，初步筛选了GC组织中的一些候选lncRNA生物标志物。通过qPCR监测GC细胞系和组织中MIR99AHG的表达水平。对我院患者和TCGA数据库病例进行生存分析。进行CCK-8测定、Transwell测定和流式细胞术以确定细胞增殖、侵袭、迁移和凋亡。同时，通过荧光素酶报告基因检测实验预测并鉴定了MIR99AHG的一个靶点。

结果

MIR99AHG在人类GC中强烈上调，并促进癌症进展。Kaplan-Meier分析显示，上调MIR99AHG表达与我院患者和TCGA数据库患者的不良总生存期（P < 0.01）呈正相关。敲低MIR99AHG表达可抑制细胞增殖、侵袭、迁移并促进细胞凋亡。此外，MIR99AHG通过竞争miR-577的内源性RNA（ceRNA）发挥致癌基因的作用。