Long noncoding RNA MAGI2-AS3 inhibits bladder cancer progression through MAGI2/PTEN/epithelial-mesenchymal transition (EMT) axis

Abstract

BACKGROUND: Long noncoding RNA (lncRNA) are critical regulators of tumor progression. OBJECTIVE: To determine how the lncRNA membrane associated guanylate kinase, WW and PDZ domain-containing 2 (MAG12) antisense RNA 3 (MAGI2-AS3) and the phosphatase and tensin homolog (PTEN) gene function in regulating bladder cancer (Bca) progression. METHODS: Total RNA from 80 and 30 paired resected Bca and para-cancerous tissues from patients with confirmed Bca was sequentially extracted, quantified, purified, and reverse transcribed using RT-PCR. A library was constructed and sequenced. Four Bca cell lines and a normal urothelial cell line were transfected with lentiviral plasmids, and cell migration and invasion were assayed in vitro. An orthotopic mouse model of Bca was created for in vivo studies. RESULTS: MAGI2-AS3 expression was significantly downregulated in Bca, compared with normal tissues, and negatively associated with tumor stage and a poor prognosis. MAGI2-AS3 and its sense RNA MAGI2 showed significant and positive correlation. The expression of MAGI2 and its downstream gene, PTEN, increased in Bca cells overexpressing MAGI2-AS3, and interference by MAGI2 expression reversed the migration and invasion inhibited by MAGI2-AS3 overexpression. CONCLUSION: MAGI2-AS3 overexpression inhibited Bca cell progression by regulating the MAGI2/PTEN/epithelial-mesenchymal transition, offering novel insights into the mechanism of Bca progression.

A New Story of the Three Magi: Scaffolding Proteins and lncRNA Suppressors of Cancer

“…All these studies report the downregulation of MAGI2-AS3 during carcinogenesis and support a role of this lncRNA as a tumor suppressor in adrenal, brain, breast, bladder, liver, lung, colorectal, prostate, pancreatic, ovarian, and renal cancers [ 208 , 209 , 210 , 213 , 214 , 217 , 220 , 222 , 223 , 230 , 232 , 234 , 235 , 236 , 237 , 238 , 239 ].…”

“…Among the putative miRNA targets, miR-200 and miR-143 are considered tumor suppressors in human bladder cancer [ 226 ]. Nevertheless, several studies have demonstrated in this cancer that MAGI2-AS3 was downregulated and negatively associated with tumor stage [ 208 , 213 , 235 ]. In this regard, Wang et al showed that low levels of MAGI2-AS3 were associated with a poor prognosis and that ectopic expression of MAGI2-AS3 inhibited proliferation, migration, and invasion of the human bladder cancer cells T24 and RT4 in vitro, and suppressed the growth of T24 cells in nude mice [ 208 ].…”

A Radioresponse-Related lncRNA Biomarker Signature for Risk Classification and Prognosis Prediction in Non-Small-Cell Lung Cancer

“…Another research studied that bladder cancer (BC) patients with upregulation of MAGI2-AS3 display a lower incidence of cancer metastasis. MAGI2-AS3 may reinforce the stability of MAGI2 to mediate epithelial-mesenchymal transition (EMT) of BC [ 51 ]. Our results are in line with these studies, suggesting the MAGI2-AS3 is a protective factor (HR < 1) in NSCLC.…”

Biological functions and clinical significance of long noncoding RNAs in bladder cancer

“…LncRNAs can directly regulate target gene expression and affect the EMT process. Overexpression of MAGI2-AS3 inhibits EMT by regulating the MAGI2/PTEN axis [ 150 ]. MIR503HG inhibits cell growth, metastasis, and EMT in BCa [ 151 ].…”

“…The MBNL1-AS1 expression level correlates with the clinical stage, tumor size, and focal classification [ 55 ]. In addition, downregulated MAGI2-AS3 correlates with the number of tumors, stage, grade, and stage [ 125 , 150 ].…”