Long Noncoding RNA MRPL23-AS1 Promotes Salivary Adenoid Cystic Carcinoma Lung Metastasis via EZH2-Mediated Transcriptional Repression of E-cadherin

Objectives: This study was to explore whether lncRNA is involved in metastasis of salivary adenoid cystic carcinoma induced by EREG.
Methods: After stably overexpressing EREG in SACC-83 cells (EREG cells) followed by microarray, qPCR, and stimulation of EREG recombinant protein validation, cancer-related long non-coding RNAs (lncRNAs) were mined. The expression of MRPL23-AS1 in salivary adenoid cystic carcinoma (SACC) was measured by qRCR. The protein expression of E-cadherin and N-cadherin in SACC cell were evaluated by western blot. Cell migration ability was measured by transwell assay. RNA-binding protein was detected by RNA-pulldown, DNA fragment was by CHIP.
Results: Bioinformatics analysis and protein stimulation showed that lncRNA MRPL23-AS1 was associated with EREG-induced SACC-progression. Moreover, the MRPL23-AS1 expression was positively correlated with EREG in SACC tissues. The knockdown of MRPL23-AS1 in EREG cells and SACC-LM cells decreased cell migration, increased expression of EMT-related factor E-cadherin, and decreased expression of N-cadherin. Through RNA-pulldown, CHIP and other experiments, it was found that lncRNA can recruit EZH2 protein and inhibit E-cadherin transcription. Exosomes derived from SACC-83 cells with stably overexpressing lncRNA were extracted and found to promote EMT and lung metastasis in vitro and in vivo.
Conclusions: LncRNA MRPL23-AS1 promotes SACC lung metastasis via EZH2-mediated transcriptional repression of E-cadherin.