Abstract
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.
Highlights
Angiogenesis is an essential physiological process in formation of new blood vessels in the human body and plays an important role in tissue growth and development as well as wound healing and tumorigenesis [1]
Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) was reported to promote cell proliferation, we further explored the effect of MALAT1 on human umbilical vein endothelial cells (HUVECs) by knockdown of MALAT1 expression using MALAT1 siRNAs
The data on the in vitro real-time cell proliferation assay showed a significant decrease in viability of si-MALAT1-transfected HUVECs compared with si-control–transfected cells (Figure 1B and 1C; P
Summary
Angiogenesis is an essential physiological process in formation of new blood vessels in the human body and plays an important role in tissue growth and development as well as wound healing and tumorigenesis [1]. Blood vessels transport oxygen and nutrients throughout the human body and nourish tumors and other disease conditions [2]. The precise mechanisms of angiogenesis remain to be defined but a large number of studies have shown that mechanical and chemical stimulation could regulate expression of different cytokine and growth factors to promote endothelial cell proliferation, while angiogenesis is the key process in www.impactjournals.com/oncotarget cancer development and progression [3]. During and after tumors have formed to a size of 1-2 mm, the blood supply cannot provide the oxygen and nutrients in order to further facilitate their growth [5]. There are several agents or antibodies used in clinical trials for treatment of various human cancers, such as lung, breast, and colorectal cancers [8, 9]
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