LncRNA MALAT1 regulates proliferation and apoptosis of vascular smooth muscle cells by targeting miRNA-124-3p/PPARα axis.

OBJECTIVE: To uncover the involvement of long non-coding RNA (lncRNA) MALAT1 in the proliferation and apoptosis of vascular smooth muscle cells (VSMCs), and the underlying mechanism. MATERIALS AND METHODS: Relative levels of MALAT1, microRNA-124-3p (miRNA-124-3p) and peroxisome proliferator-activated receptor alpha (PPARα) in VSMCs treated with different doses of oxidized low-density lipoprotein (ox-LDL) for different time points were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Proliferative and apoptotic changes of VSMCs overexpressing MALAT1 were assessed. Subcellular distribution of MALAT1 was analyzed. The potential binding among MALAT1, miRNA-124-3p and PPARα was determined by dual-luciferase reporter gene assay, and their interaction was determined as well. Finally, the influences of MALAT1/miRNA-124-3p/PPARα regulatory loop on the proliferative and apoptotic abilities of VSMCs were examined. RESULTS: MALAT1 and PPARα were dose-dependently downregulated in ox-LDL-treated VSMCs, whereas miRNA-124-3p was gradually upregulated. Overexpression of MALAT1 attenuated viability and induced apoptosis in ox-LDL-treated VSMCs. Moreover, MALAT1 was mainly distributed in the nucleus. Dual-luciferase reporter gene assay verified that MALAT1 could sponge miRNA-124-3p, and moreover, PPARα was the direct target of miRNA-124-3p. MALAT1 negatively regulated miRNA-124-3p level and miRNA-124-3p negatively regulated PPARα level as well. Finally, MALAT1/miRNA-124-3p/PPARα regulatory loop was identified to regulate the viability and apoptosis of ox-LDL-treated VSMCs. CONCLUSIONS: LncRNA MALAT1 mediates proliferation and apoptosis of VSMCs by sponging miRNA-124-3p to positively regulate PPARα level.

Reduced miR-300 expression predicts poor prognosis in patients with laryngeal squamous cell carcinoma.

OBJECTIVE: miR-300 has been demonstrated to play an important role in the progression of several tumors, but its role in tumorigenesis of laryngeal squamous cell carcinoma (LSCC) is still unclear. The purpose of this study was to explore miR-300 expression in LSCC patients and analyze its association with clinicopathological factors and prognosis. PATIENTS AND METHODS: In the present study, we measured the expression level of miR-300 in LSCC tissues by RT-PCR. Associations between miRNA-300 expressions and various clinicopathological characteristics were analyzed. Patient survival and their differences were determined by Kaplan-Meier method and log-rank test. The univariate and multivariate analysis were performed using the Cox proportional hazard analysis. RESULTS: miR-300 expression was significantly increased in LSCC tissues compared with that in adjacent non-cancerous tissues (p < 0.01). In addition, lymph node metastasis (p = 0.004) and TNM stage (p = 0.001) were obvious influence factors for the expression of miR-300. More importantly, Kaplan-Meier analysis showed that LSCC patients with low miR-300 expression tended to have shorter overall survival (p < 0.001). Finally, multivariate analysis revealed that miR-300 expression was an independent prognostic factor for LSCC patients. CONCLUSIONS: Our results pointed to miR-300 as a powerful prognostic marker in LSCC and as a novel target for tumor-suppressive therapy.