Dataset Information

Lnc-NA inhibits proliferation and metastasis in endometrioid endometrial carcinoma through regulation of NR4A1.

ABSTRACT: Endometrioid endometrial carcinoma (EEC) is the most common gynaecologic malignancy worldwide. Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, particularly cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in EEC have not been extensively studied. Here, we describe the discovery of Lnc-NA from the promoter of the transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) gene. The role and function of Lnc-NA in EEC remain unknown. In this study, we used quantitative real-time polymerase chain reactions to confirm that Lnc-NA expression was down-regulated in 30 EEC cases (90%) and in EEC cell lines compared with that in the paired adjacent tissues and normal endometrial cells. In vitro experiments further demonstrated that overexpressing Lnc-NA decreased EEC cell proliferation, migration and invasion and promoted apoptosis via inactivation of the apoptosis signalling pathway. Moreover, the results show that Lnc-NA expression was positively correlated with NR4A1. Furthermore, Lnc-NA regulated NR4A1 expression and activated the apoptosis signalling pathway to inhibit tumour progression. In summary, our results demonstrate that the Lnc-NA-NR4A1 axis could be a useful tumour suppressor and a promising therapeutic target for EEC.

SUBMITTER: Sun L

PROVIDER: S-EPMC6584524 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Lnc-NA inhibits proliferation and metastasis in endometrioid endometrial carcinoma through regulation of NR4A1.

Sun Linying L Zhou Rongfang R Dong Jing J Liu Shuang S Jiao Yulian Y Wang Laicheng L Hu Shengnan S He Pengjuan P Liu Xiaowen X Zhao Xingbo X Jiang Guosheng G Zhao Yueran Y

Journal of cellular and molecular medicine 20190503 7

Endometrioid endometrial carcinoma (EEC) is the most common gynaecologic malignancy worldwide. Long non-coding RNAs have previously been demonstrated to play important roles in regulating human diseases, particularly cancer. However, the biological functions and molecular mechanisms of long non-coding RNAs in EEC have not been extensively studied. Here, we describe the discovery of Lnc-NA from the promoter of the transcription factor nuclear receptor subfamily 4 group A member 1 (NR4A1) gene. Th ...[more]

PMID: 31050196

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Project description:BACKGROUND: It has been recognized cancer cells acquire characters reminiscent of those of normal stem cells, and the degree of stem cell gene expression correlates with patient prognosis. Lgr5(+) or CD133(+) epithelial stem cells (EpiSCs) have recently been identified and these cells are susceptible to neoplastic transformation. It is unclear, however, whether genes enriched in EpiSCs also contribute in tumor malignancy. Endometrial endometrioid carcinoma (EEC) is a dominant type of the endometrial cancers and is still among the most common female cancers. Clinically endometrial carcinoma is classified into 4 FIGO stages by the degree of tumor invasion and metastasis, and the survival rate is low in patients with higher stages of tumors. Identifying genes shared between advanced tumors and stem cells will not only unmask the mechanisms of tumor malignancy but also provide novel therapeutic targets. RESULTS: To identify EpiSC genes in late (stages III-IV) EECs, a molecular signature distinguishing early (stages I-II) and late EECs was first identified to delineate late EECs at the genomics level. ERBB2 and CCR1 were genes activated in late EECs, while APBA2 (MINT2) and CDK inhibitor p16 tumor suppressors in early EECs. MAPK pathway was significantly up in late EECs, indicating drugs targeting this canonical pathway might be useful for treating advanced EECs. A six-gene mini-signature was further identified to differentiate early from advanced EECs in both the training and testing datasets. Advanced, invasive EECs possessed a clear EpiSC gene expression pattern, explaining partly why these tumors are more malignant. CONCLUSIONS: Our work provides new insights into the pathogenesis of EECs and reveals a previously unknown link between adult stem cells and the histopathological traits of EECs. Shared EpiSC genes in late EECs may contribute to the stem cell-like phenotypes shown by advanced tumors and hold the potential of being candidate therapeutic targets and novel prognosis biomarkers.

Dataset Information

Lnc-NA inhibits proliferation and metastasis in endometrioid endometrial carcinoma through regulation of NR4A1.

Publications

Lnc-NA inhibits proliferation and metastasis in endometrioid endometrial carcinoma through regulation of NR4A1.

Similar Datasets

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