LncRNA TUG1 regulates ApoM to promote atherosclerosis progression through miR-92a/FXR1 axis.

Abstract

This study aims to explore the possible mechanism of TUG1 regulating ApoM in AS. To this end, expression levels of TUG1 and ApoM were measured in high fat dieted C57BL/6J mice, normal dieted C57BL/6J mice, ob/ob mice and db/db mice. LV‐TUG1 or sh‐TUG1 was injected into C57BL/6J mice before isolating peritoneal macrophages to measure cholesterol efflux (CE) and expression levels of ABCA1, ABCG1 and SR‐BI. Meanwhile, CE in RAW264.7 cells was also measured after cell transfection. Dual luciferase reporter assay and anti‐AGO2 RIP were applied to verify the relationship among TUG1, FXR1 and miR‐92a. Total cholesterol (TC), triglyceride (TG), low‐density lipoprotein cholesterin (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C) as well as expressions of inflammatory cytokines (TNF‐α, IL‐1β and IL‐6) in plasma were measured. Knock‐down or expressed TUG1, FXR1 or miR‐92a in NCTC 1469 cells or in ApoE−/− AS mice to determine the alteration on ApoM and plaque size. TUG1 was highly expressed while ApoM was down‐regulated in high fat dieted C57BL/6J mice, b/ob and db/db mice. Overexpression of TUG1 could reduce the expression of ApoM, ABCA1 and ABCG1 in addition to slowing down CE rate. Reversed expression pattern was found in cells with knock‐down of TUG1. TUG1 can compete with FXR1 to bind miR‐92a. FXR1 negatively target ApoM. Overexpression of TUG1 in ApoE−/− mice can increase plaque size and enhance macrophage contents accordingly. TUG1 can inhibit ApoM in both liver tissues and plasma to inhibit CE through regulating miR‐92a/ FXR1 axis. TUG1 is a promising target for AS treatment.