期刊
CANCER LETTERS
卷 490, 期 -, 页码 111-123出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2020.07.012
关键词
Pseudogene; LGMNP1; CeRNA; MiR-495-3p; Glioblastoma
类别
资金
- National Natural Science Foundation of China [81671203, 81874215, 81803041, 81772654]
- Shanghai Sailing Program [20YF1426200]
- Shanghai Science and Technology [201409002400, 201409003000]
- Cultivation Project of Renji Hospital South Campus, School of Medicine, Shanghai Jiaotong University [2019GZRPYQN01]
- Youth program of Wuxi health commission [Q201923]
- General Programs of Nanjing Medical University [2017NJMU172]
- Anhui Provincial Natural Science Foundation [1808085QH287]
Pseudogenes, which are long noncoding RNAs that originate from protein-coding genes, have been suggested to play important roles in disease. Although studies have revealed high expression of legumain (LGMN) in many types of tumors, the regulation of LGMN remains largely unknown. Here, we found that a novel LGMN pseudogene (LGMNP1) was upregulated in glioblastoma (GBM) tissues and high LGMNP1 expression in GBM cells enhanced proliferation and invasion. Biochemical analysis showed that cytoplasmic LGMNP1 functionally tar geted miR-495-3p in a manner involving an RNA-induced silencing complex. Dual-luciferase reporter assays demonstrated that LGMN was a target of miR-495-3p, and LGMN was upregulated and positively correlated with LGMNP1 in GBM. Moreover, miR-495-3p was downregulated and negatively correlated with LGMNP1 in GBM tissues. Notably, the tumor-promoting effects of LGMNP1 upregulation could be alleviated by miR-495-3p mimics. Furthermore, GBM cells overexpressing LGMNP1 exhibited more aggressive tumor progression and elevated LGMN expression in vivo. Thus, our data illustrate that LGMNP1 exerts its oncogenic activity, at least in part, as a competitive endogenous RNA (ceRNA) that elevates LGMN expression by sponging miR-495-3p. CeRNA-mediated miRNA sequestration might be a novel therapeutic strategy in GBM.
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