Research Papers:

Knockdown of MALAT1 expression inhibits HUVEC proliferation by upregulation of miR-320a and downregulation of FOXM1 expression

Jian-Yong Sun, Zheng-Wei Zhao, Wei-Miao Li, Guang Yang, Peng-Yu Jing, Pei Li, Hai-Zhou Dang, Zhao Chen, Yong-An Zhou and Xiao-Fei Li _

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Oncotarget. 2017; 8:61499-61509. https://doi.org/10.18632/oncotarget.18507

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Jian-Yong Sun1,*, Zheng-Wei Zhao1,*, Wei-Miao Li1,2,*, Guang Yang1, Peng-Yu Jing1, Pei Li1, Hai-Zhou Dang1, Zhao Chen1, Yong-An Zhou1 and Xiao-Fei Li1

1Department of Thoracic Surgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China

2Department of Respiration, Tangdu Hospital, Fourth Military Medical University, Xi’an, Shaanxi, China

*These authors have contributed equally to this work

Correspondence to:

Xiao-Fei Li, email: lixfchest@163.com

Yong-An Zhou, email: chuyan22@fmmu.edu.cn

Keywords: MALAT1, HUVECs, proliferation, miR-320a, FOXM1

Received: March 20, 2017    Accepted: May 21, 2017    Published: June 16, 2017


Regulation of cancer angiogenesis could be a useful strategy in cancer therapy. Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA), and can induce cancer cell proliferation, while lncRNAs, generally are able to act as microRNA (miRNA) sponges. The latter is a type of competitive endogenous RNA (ceRNA) that regulates expression of the targeting miRNAs and protein-coding genes. This study investigated the proliferative role of MALAT1 in human umbilical vein endothelial cells (HUVECs) and the underlying molecular events. The data showed that knockdown of MALAT1 expression using MALAT1 siRNA inhibited HUVEC proliferation and also significantly decreased levels of FOXM1 mRNA and protein in vitro, while knockdown of FOXM1 expression reduced HUVEC proliferation. Annotation of HUVEC microarray data revealed that seven miRNAs, including miR-320a, were upregulated after knockdown of MALAT1 expression in HUVECs. MALAT1 was shown to reciprocally interact with miR-320a, i.e., expression of one negatively regulated levels of the other, whereas knockdown of MALAT1 expression promoted miR-320a levels. Furthermore, miR-320a could directly target and inhibit FOXM1 expression in HUVECs. Knockdown of MALAT1 expression enhanced miR-320a expression but reduced FOXM1 expression resulting in downregulation of HUVEC proliferation. However, such an effect was inhibited by miR-320a depletion. In conclusion, this study demonstrates that miR-320a plays an important role in mediating the effects of MALAT1 on HUVEC proliferation by suppression of FOXM1 expression. Thus, targeting of this gene pathway could be a novel strategy in cancer therapy.

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