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

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.

Reduced expression of microRNA‑199a‑3p is associated with vascular endothelial cell injury induced by type 2 diabetes mellitus

“…MiR-30b regulates transforming growth factor-β2 expression to influence the ability of HUVECS to form tubes in vitro (29). MiR-98 inhibits low-density lipoprotein (LDL)-induced vascular endothelial cell injury by targeting lectin-like oxidized LDL receptor-1 gene expression (30), while miR-320a overexpression promotes the proliferation of vascular endothelial cells (31). In the present study, it was determined that miR-199a-3p downregulation in patients with T2DM was associated with diabetic angiopathy.…”

The role of lncRNA MALAT1 in cardiovascular disease

“…In addition, MALAT1 also protected HCAECs against ox‐LDL induced apoptosis via sponging miR‐155 targeting suppressor of cytokine‐signaling‐1 (SOCS1) . In contrast, MALAT1 was found to promote the apoptosis of cardiomyocytes line HL‐1 or H9C2 under the H/R condition via sponging miR‐145a, miR‐144, or miR‐320 . MALAT1 promoted hypoxia‐induced apoptosis of myocardial cells by sponging miR‐200a‐3p, which targeted programmed cell death 4 (PDCD4) …”

Suppression of Hepatocellular Carcinoma Progression through FOXM1 and EMT Inhibition via Hydroxygenkwanin-Induced miR-320a Expression

“…MiRNAs are one of the main regulators of gene transcription, and previous studies have already shown that FOXM1 expression can be regulated by miR-320a [36,37]. To determine if HGK regulates FOXM1 expression by regulating miR-320a, real-time RT-PCR was used to analyze miR-320a expression in HGK-treated Huh7 and HepG2 cells.…”